View source for Biology:Retina

{{short description|Part of the eye}}
{{for multi|the electronics screen trademark|Retina display|other uses}}
{{Infobox anatomy
| Name        = Retina
| pronunciation = {{IPAc-en|UK|ˈ|r|ɛ|t|ɪ|n|ə}},<br />{{IPAc-en|US|ˈ|r|ɛ|t|ən|ə}},<br />pl. retinae {{IPAc-en|-|n|i}}
| Latin       = rēte, tunica interna bulbi
| Image       = Human eye cross-sectional view grayscale.png
| Caption     = Right [[Biology:Human eye|human eye]] cross-sectional view; eyes vary significantly among animals.
| Width       =
| Image2      =
| Caption2    =
| Precursor   =
| part_of     = [[Biology:Eye|Eye]]
| System      = [[Biology:Visual system|Visual system]]
| Artery      = Central retinal artery
| Vein        =
| Nerve       =
| Lymph       =
}}

The '''retina''' ({{etymology|la|{{wiktlat|rete}}|net}}; {{plural abbr|'''retinae'''}} or '''retinas''') is the innermost, [[Medicine:Photosensitivity|light-sensitive]] layer of [[Biology:Tissue|tissue]] of the [[Biology:Eye|eye]] of most [[Biology:Vertebrate|vertebrate]]s and some [[Biology:Mollusca|molluscs]]. The optics of the eye create a [[Physics:Focus (optics)|focused]] two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the [[Biology:Optic nerve|optic nerve]] to the [[Biology:Visual cortex|visual cortex]] to create [[Philosophy:Visual perception|visual perception]]. The retina serves a function which is in many ways analogous to that of the [[Engineering:Photographic film|film]] or [[Engineering:Image sensor|image sensor]] in a [[Physics:Camera|camera]].

The neural retina consists of several layers of [[Biology:Neuron|neuron]]s interconnected by [[Biology:Chemical synapse|synapses]] and is supported by an outer layer of pigmented epithelial cells. The primary light-sensing cells in the retina are the [[Biology:Photoreceptor cell|photoreceptor cell]]s, which are of two types: [[Biology:Rod cell|rods]] and [[Biology:Cone cell|cones]]. Rods function mainly in dim light and provide monochromatic vision. Cones function in well-lit conditions and are responsible for the perception of colour through the use of a range of [[Biology:Opsin|opsins]], as well as high-acuity vision used for tasks such as reading. A third type of light-sensing cell, the [[Biology:Intrinsically photosensitive retinal ganglion cells|photosensitive ganglion cell]], is important for entrainment of [[Biology:Circadian rhythm|circadian rhythm]]s and reflexive responses such as the [[Biology:Pupillary light reflex|pupillary light reflex]].

Light striking the retina initiates a cascade of chemical and electrical events that ultimately trigger nerve impulses that are sent to various visual centres of the [[Biology:Brain|brain]] through the fibres of the [[Biology:Optic nerve|optic nerve]]. Neural signals from the rods and cones undergo processing by other neurons, whose output takes the form of [[Biology:Action potential|action potential]]s in [[Biology:Retinal ganglion cell|retinal ganglion cell]]s whose [[Biology:Axon|axon]]s form the optic nerve.<ref>{{Cite book |title = Krause's Essential Human Histology for Medical Students |last = J |first = Krause William |year=2005 |publisher = Universal Publishers |isbn = 978-1-58112-468-2 |location = Boca Raton, FL|language = en }}</ref> 

In vertebrate [[Biology:Embryonic development|embryonic development]], the retina and the optic nerve originate as outgrowths of the developing brain, specifically the embryonic [[Biology:Diencephalon|diencephalon]]; thus, the retina is considered part of the [[Biology:Central nervous system|central nervous system]] (CNS) and is actually brain tissue.<ref name="eb">"Sensory Reception: Human Vision: Structure and function of the Human Eye" vol. 27, Encyclopædia Britannica, 1987</ref><ref>{{cite press release |title=Penn Researchers Calculate How Much the Eye Tells the Brain |url=http://www.uphs.upenn.edu/news/News_Releases/jul06/retinput.htm |date=26 July 2006 |url-status=dead |archive-url=https://web.archive.org/web/20130311163145/http://www.uphs.upenn.edu/news/News_Releases/jul06/retinput.htm |archive-date=11 March 2013 |publisher=PENN Medicine |access-date=22 April 2022}}</ref> It is the only part of the CNS that can be visualized noninvasively. Like most of the brain, the retina is isolated from the vascular system by the [[Biology:Blood–brain barrier|blood–brain barrier]]. The retina is the part of the body with the greatest continuous energy demand.<ref name="Viegas Neuhauss">{{cite journal | last1=Viegas | first1=Filipe O. | last2=Neuhauss | first2=Stephan C. F. | title=A Metabolic Landscape for Maintaining Retina Integrity and Function | journal=Frontiers in Molecular Neuroscience |  volume=14 | date=2021 | issn=1662-5099 | doi=10.3389/fnmol.2021.656000 | page= | pmid=33935647 | pmc=8081888 | doi-access=free }}</ref>

== Structure ==

=== Inverted versus non-inverted retina ===
The vertebrate retina is ''inverted'' in the sense that the light-sensing cells are in the back of the retina, so that light has to pass through layers of neurons and capillaries before it reaches the photosensitive sections of the rods and cones.<ref name="Kolb"/> The ganglion cells, whose axons form the optic nerve, are at the front of the retina; therefore, the optic nerve must cross through the retina en route to the brain. No photoreceptors are in this region, giving rise to the [[Biology:Blind spot (vision)|blind spot]].<ref>{{cite web|last1=Kolb|first1=Helga|title=Photoreceptors|url=https://webvision.med.utah.edu/book/part-ii-anatomy-and-physiology-of-the-retina/photoreceptors/|website=Webvision|access-date=11 January 2018}}</ref> In contrast, in the [[Biology:Cephalopod|cephalopod]] retina, the photoreceptors are in front, with processing neurons and capillaries behind them. Because of this, cephalopods do not have a blind spot.

Although the overlying neural tissue is partly transparent, and the accompanying glial cells have been shown to act as [[Engineering:Optical fiber|fibre-optic]] channels to transport photons directly to the photoreceptors,<ref name="pmid17485670">{{cite journal |vauthors = Franze K, Grosche J, Skatchkov SN, Schinkinger S, Foja C, Schild D, Uckermann O, Travis K, Reichenbach A, Guck J |title = Muller cells are living optical fibers in the vertebrate retina |journal = Proc. Natl. Acad. Sci. U.S.A. |volume = 104 |issue = 20 |pages = 8287–8292 |year = 2007 |pmid = 17485670 |pmc = 1895942 |doi = 10.1073/pnas.0611180104 |bibcode = 2007PNAS..104.8287F |doi-access = free }}</ref><ref>{{cite magazine|last1=Baker|first1=Oliver|title=Focus: Eye Cells as Light Pipes|magazine=Physical Review Focus|date=23 April 2010|volume=25|issue=15|doi=10.1103/physrevfocus.25.15}}</ref> light scattering does occur.<ref name="Bringmann2018">{{cite journal | vauthors = Bringmann A, Syrbe S, Görner K, Kacza J, Francke M, Wiedemann P, Reichenbach A | title = The primate fovea: Structure, function and development | journal = Prog Retin Eye Res | volume = 66 | pages = 49–84 | date = 2018 | pmid = 29609042 | doi = 10.1016/j.preteyeres.2018.03.006 | s2cid = 5045660 }}</ref> Some vertebrates, including humans, have an area of the central retina adapted for high-acuity vision. This area, termed the [[Medicine:Fovea centralis|fovea centralis]], is avascular (does not have blood vessels), and has minimal neural tissue in front of the photoreceptors, thereby minimizing light scattering.<ref name="Bringmann2018"/>

The cephalopods have a non-inverted retina, which is comparable in [[Angular resolution|resolving power]] to the eyes of many vertebrates. Squid eyes do not have an analog of the vertebrate [[Medicine:Retinal pigment epithelium|retinal pigment epithelium]] (RPE). Although their photoreceptors contain a protein, retinochrome, that recycles retinal and replicates one of the functions of the vertebrate RPE, cephalopod photoreceptors are likely not maintained as well as in vertebrates, and that as a result, the useful lifetime of photoreceptors in invertebrates is much shorter than in vertebrates.<ref>{{Cite journal |last1 = Sperling |first1 = L. |last2 = Hubbard |first2 = R. |date = 1 February 1975 |title = Squid retinochrome. |journal = The Journal of General Physiology |volume = 65 |issue = 2 |pages = 235–251 |doi = 10.1085/jgp.65.2.235 |issn = 0022-1295 |pmid = 235007 |pmc=2214869}}</ref> Having easily replaced stalk eyes (some lobsters) or retinae (some spiders, such as'' Deinopis''<ref>{{cite web |url = https://australian.museum/learn/animals/spiders/how-spiders-see-the-world/ |title = How spiders see the world – Australian Museum |website = www.australian.museum |access-date = 5 December 2017 |url-status = live |archive-url = https://web.archive.org/web/20170912224747/https://australianmuseum.net.au/how-spiders-see-the-world |archive-date = 12 September 2017 }}</ref>) rarely occurs.

The cephalopod retina does not originate as an outgrowth of the brain, as the vertebrate one does. This difference suggests that vertebrate and cephalopod eyes are not [[Biology:Homology|homologous]], but have evolved separately. From an evolutionary perspective, a more complex structure such as the inverted retina can generally come about as a consequence of two alternate processes - an advantageous "good" compromise between competing functional limitations, or as a historical maladaptive relic of the convoluted path of organ evolution and transformation. Vision is an important adaptation in higher vertebrates.

A third view of the "inverted" vertebrate eye is that it combines two benefits - the maintenance of the photoreceptors mentioned above, and the reduction in light intensity necessary to avoid blinding the photoreceptors, which are based on the extremely sensitive eyes of the ancestors of modern hagfish (fish that live in very deep, dark water).<ref>{{cite journal |title=Metabolism and enzyme activities of hagfish from shallow and deep water of the Pacific Ocean |date=June 2011 |volume=159 |issue=2 |pages=182–187 |journal=Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology |doi=10.1016/j.cbpa.2011.02.018 |pmid=21356325 |last1=Drazen |first1=J. C. |last2=Yeh |first2=J. |last3=Friedman |first3=J. |last4=Condon |first4=N. }}</ref>

A recent study on the evolutionary purpose for the inverted retina structure from the APS (American Physical Society)<ref>{{Cite journal |last1=Labin |first1=A. M. |last2=Ribak |first2=E. N. |date=2010-04-16 |title=Retinal Glial Cells Enhance Human Vision Acuity |url=https://link.aps.org/doi/10.1103/PhysRevLett.104.158102 |journal=Physical Review Letters |volume=104 |issue=15 |pages=158102 |doi=10.1103/PhysRevLett.104.158102|pmid=20482021 |bibcode=2010PhRvL.104o8102L }}</ref> says that "The directional of glial cells helps increase the clarity of human vision. But we also noticed something rather curious: the colours that best passed through the glial cells were green to red, which the eye needs most for daytime vision. The eye usually receives too much blue—and thus has fewer blue-sensitive cones.

Further computer simulations showed that green and red are concentrated five to ten times more by the glial cells, and into their respective cones, than blue light. Instead, excess blue light gets scattered to the surrounding rods. This optimization is such that color vision during the day is enhanced, while night-time vision suffers very little".

=== Retinal layers ===
[[File:Gray881.png|thumb|upright=1.36|Section of retina]]
[[File:Retina-diagram.svg|thumb|upright=1.35|Rods, cones, and nerve layers in the retina: The front (anterior) of the eye is on the left. Light (from the left) passes through several transparent nerve layers to reach the rods and cones (far right). Chemical changes in the rods and cones send a signal back to the nerves. The signal goes first to the bipolar and horizontal cells (yellow layer), then to the amacrine cells and ganglion cells (purple layer), then to the optic nerve fibres. The signals are processed in these layers. First, the signals start as raw outputs of points in the rod and cone cells. Then, the nerve layers identify simple shapes, such as bright points surrounded by dark points, edges, and movement. (Based on a drawing by Ramón y Cajal, 1911)]]
[[File:ConeMosaics.jpg|thumb|upright=1.36|Illustration of the distribution of cone cells in the fovea of an individual with normal colour vision (left), and a colourblind (protanopic) retina. The center of the fovea holds very few blue-sensitive cones.]]
[[File:Human photoreceptor distribution.svg|thumb|upright=1.36|Distribution of rods and cones along a line passing through the fovea and the blind spot of a human eye<ref>[https://stanford.edu/group/vista/cgi-bin/FOV/chapter-3-the-photoreceptor-mosaic Foundations of Vision] {{webarchive|url=https://web.archive.org/web/20131203022748/http://stanford.edu/group/vista/cgi-bin/FOV/chapter-3-the-photoreceptor-mosaic |date=3 December 2013 }}, Brian A. Wandell</ref>]]

The vertebrate retina has 10 distinct layers.<ref>{{cite web|url=http://education.vetmed.vt.edu/Curriculum/VM8054/EYE/RETINA.HTM |title=The Retinal Tunic |archive-url=https://web.archive.org/web/20070518033845/http://education.vetmed.vt.edu/Curriculum/VM8054/EYE/RETINA.HTM |archive-date=18 May 2007 |url-status=dead |website=Virginia–Maryland Regional College of Veterinary Medicine}}</ref> From closest to farthest from the vitreous body:

# [[Medicine:Inner limiting membrane|Inner limiting membrane]] – basement membrane elaborated by [[Biology:Muller glia|Müller cells]]
# [[Medicine:Nerve fiber layer|Nerve fibre layer]] – axons of the [[Biology:Retinal ganglion cell|ganglion cell]] bodies (a thin layer of Müller cell footplates exists between this layer and the inner limiting membrane)
# [[Medicine:Ganglion cell layer|Ganglion cell layer]] – contains nuclei of ganglion cells, the axons of which become the optic nerve fibres, and some displaced amacrine cells<ref name="eb" />
# [[Medicine:Inner plexiform layer|Inner plexiform layer]] – contains the synapse between the [[Biology:Retina bipolar cell|bipolar cell]] axons and the dendrites of the [[Biology:Retinal ganglion cell|ganglion]] and amacrine cells<ref name="eb" />
# [[Medicine:Inner nuclear layer|Inner nuclear layer]] – contains the nuclei and surrounding cell bodies (perikarya) of the amacrine cells, [[Biology:Retina bipolar cell|bipolar cells]], and [[Biology:Retina horizontal cell|horizontal cells]]<ref name="eb" />
# [[Medicine:Outer plexiform layer|Outer plexiform layer]] – projections of rods and cones ending in the rod spherule and cone pedicle, respectively, these make synapses with dendrites of bipolar cells and horizontal cells.<ref name="eb" /> In the [[Medicine:Macula|macula]]r region, this is known as the ''Fiber layer of Henle''.
# [[Medicine:Outer nuclear layer|Outer nuclear layer]] – cell bodies of rods and cones
# [[Medicine:External limiting membrane|External limiting membrane]] – layer that separates the inner segment portions of the photoreceptors from their cell nuclei
# [[Medicine:Layer of rods and cones|Inner segment / outer segment layer]] – inner segments and outer segments of rods and cones, the outer segments contain a highly specialized light-sensing apparatus.<ref>{{cite journal | vauthors = Goldberg AF, Moritz OL, Williams DS | title = Molecular basis for photoreceptor outer segment architecture | journal = Prog Retin Eye Res | volume = 55 | pages = 52–81 | date = 2016 | pmid = 27260426 | pmc = 5112118 | doi = 10.1016/j.preteyeres.2016.05.003}}</ref><ref>{{cite journal | vauthors = Arshavsky VY, Burns ME | title = Photoreceptor signaling: supporting vision across a wide range of light intensities | journal = J Biol Chem | volume = 287 | issue = 3 | pages = 1620–1626 | date = 2012 | pmid = 22074925 | pmc = 3265842 | doi = 10.1074/jbc.R111.305243| doi-access = free }}</ref> 
# [[Medicine:Retinal pigment epithelium|Retinal pigment epithelium]] – single layer of cuboidal epithelial cells (with extrusions not shown in diagram). This layer is closest to the choroid, and provides nourishment and supportive functions to the neural retina, The black pigment melanin in the pigment layer prevents light reflection throughout the globe of the eyeball; this is extremely important for clear vision.<ref name="Guyton and Hall Physiology">{{Cite book|title=Guyton and Hall Physiology|pages=612}}</ref><ref>{{cite journal | vauthors = Sparrow JR, Hicks D, Hamel CP | title = The retinal pigment epithelium in health and disease | journal = Curr Mol Med | volume = 10 | issue = 9 | pages = 802–823 | date = 2010 | pmid = 21091424 | pmc = 4120883| doi = 10.2174/156652410793937813 }}</ref><ref>{{cite journal | vauthors = Letelier J, Bovolenta P, Martínez-Morales JR | title = The pigmented epithelium, a bright partner against photoreceptor degeneration | journal = J Neurogenet | volume = 31 | issue = 4 | pages = 203–215 | date = 2017 | pmid = 29113536 | doi = 10.1080/01677063.2017.1395876| s2cid = 1351539 }}</ref>

These layers can be grouped into four main processing stages—photoreception; transmission to [[Biology:Retina bipolar cell|bipolar cells]]; transmission to [[Biology:Retinal ganglion cell|ganglion cells]], which also contain photoreceptors, the photosensitive ganglion cells; and transmission along the optic nerve. At each synaptic stage,  [[Biology:Retina horizontal cell|horizontal]] and amacrine cells also are laterally connected.

The [[Biology:Optic nerve|optic nerve]] is a central tract of many axons of ganglion cells connecting primarily to the lateral geniculate body, a visual relay station in the [[Biology:Diencephalon|diencephalon]] (the rear of the forebrain). It also projects to the [[Biology:Superior colliculus|superior colliculus]], the [[Biology:Suprachiasmatic nucleus|suprachiasmatic nucleus]], and the nucleus of the optic tract. It passes through the other layers, creating the [[Medicine:Optic disc|optic disc]] in primates.<ref>{{cite book |author = Shepherd, Gordon |year = 2004 |title = The Synaptic Organization of the Brain |url = https://archive.org/details/synapticorganiza00mdgo_475 |url-access = limited |publisher = Oxford University Press |location = New York |pages = [https://archive.org/details/synapticorganiza00mdgo_475/page/n233 217]–225 |isbn = 978-0-19-515956-1 }}</ref>

Additional structures, not directly associated with vision, are found as outgrowths of the retina in some vertebrate groups. In [[Biology:Bird|bird]]s, the [[Biology:Pecten oculi|pecten]] is a vascular structure of complex shape that projects from the retina into the vitreous humour; it supplies oxygen and nutrients to the eye, and may also aid in vision. [[Biology:Reptile|Reptile]]s have a similar, but much simpler, structure.<ref name=VB>{{cite book |author = Romer, Alfred Sherwood |author2 = Parsons, Thomas S. |year = 1977 |title = The Vertebrate Body |publisher = Holt-Saunders International |location = Philadelphia, PA |page = 465 |isbn = 978-0-03-910284-5 }}</ref>

In adult humans, the entire retina is about 72% of a sphere about 22&nbsp;mm in diameter. The entire retina contains about 7 million cones and 75 to 150 million rods. The optic disc, a part of the retina sometimes called "the blind spot" because it lacks photoreceptors, is located at the [[Medicine:Optic disc|optic papilla]], where the optic-nerve fibres leave the eye. It appears as an oval white area of 3&nbsp;mm<sup>2</sup>. Temporal (in the direction of the temples) to this disc is the [[Medicine:Macula|macula]], at whose centre is the [[Medicine:Fovea centralis|fovea]], a pit that is responsible for sharp central vision, but is actually less sensitive to light because of its lack of rods. Human and non-human [[Biology:Primate|primate]]s possess one fovea, as opposed to certain bird species, such as hawks, that are bifoviate, and dogs and cats, that possess no fovea, but a central band known as the visual streak.{{citation needed|date=March 2018|reason=Citations are needed for some of these statements, esp. bifoviate hawks and the lack of fovea in cats and dogs}} Around the fovea extends the central retina for about 6&nbsp;mm and then the peripheral retina. The farthest edge of the retina is defined by the [[Medicine:Ora serrata|ora serrata]]. The distance from one ora to the other (or macula), the most sensitive area along the horizontal meridian, is about 32&nbsp;mm.{{clarify|date=April 2018|reason=sentence is confusing; is all the area between the ora the macula, and are we talking length of curvature or that of a straight line?}}

In section, the retina is no more than 0.5&nbsp;mm thick. It has three layers of [[Biology:Nerve|nerve]] cells and two of [[Biology:Synapse|synapse]]s, including the unique [[Biology:Ribbon synapse|ribbon synapse]]. The optic nerve carries the [[Biology:Retinal ganglion cell|ganglion-cell]] [[Biology:Axon|axon]]s to the brain, and the blood vessels that supply the retina. The ganglion cells lie innermost in the eye while the photoreceptive cells lie beyond. Because of this counter-intuitive arrangement, light must first pass through and around the ganglion cells and through the thickness of the retina, (including its capillary vessels, not shown) before reaching the rods and cones. Light is absorbed by the [[Medicine:Retinal pigment epithelium|retinal pigment epithelium]] or the [[Biology:Choroid|choroid]] (both of which are opaque).

The [[Biology:White blood cell|white blood cell]]s in the capillaries in front of the photoreceptors can be perceived as tiny bright moving dots when looking into blue light. This is known as the [[Physics:Blue field entoptic phenomenon|blue field entoptic phenomenon]] (or Scheerer's phenomenon).

Between the [[Biology:Retinal ganglion cell|ganglion-cell]] layer and the rods and cones are two layers of [[Biology:Neuropil|neuropil]]s, where synaptic contacts are made. The neuropil layers are the [[Medicine:Outer plexiform layer|outer plexiform layer]] and the [[Medicine:Inner plexiform layer|inner plexiform layer]]. In the outer neuropil layer, the rods and cones connect to the vertically running [[Biology:Retina bipolar cell|bipolar cells]], and the horizontally oriented [[Biology:Retina horizontal cell|horizontal cells]] connect to ganglion cells.

The central retina predominantly contains cones, while the peripheral retina predominantly contains rods. In total, the retina has about seven million cones and a hundred million rods. At the centre of the macula is the foveal pit where the cones are narrow and long, and arranged in a hexagonal [[Biology:Retinal mosaic|mosaic]], the most dense, in contradistinction to the much fatter cones located more peripherally in the retina.<ref name="ReferenceA">{{Cite book|title=Guyton and Hall Physiology|pages=609}}</ref> At the foveal pit, the other retinal layers are displaced, before building up along the foveal slope until the rim of the fovea, or [[Biology:Parafovea|parafovea]], is reached, which is the thickest portion of the retina. The macula has a yellow pigmentation, from screening pigments, and is known as the macula lutea. The area directly surrounding the fovea has the highest density of rods converging on single bipolar cells. Since its cones have a much lesser convergence of signals, the fovea allows for the sharpest vision the eye can attain.<ref name="eb" />

Though the rod and cones are a [[Biology:Retinal mosaic|mosaic]] of sorts, transmission from receptors, to bipolars, to [[Biology:Retinal ganglion cell|ganglion cells]] is not direct. Since about 150 million receptors and only 1 million optic nerve fibres exist, convergence and thus mixing of signals must occur. Moreover, the horizontal action of the [[Biology:Retina horizontal cell|horizontal]] and amacrine cells can allow one area of the retina to control another (e.g. one stimulus inhibiting another). This inhibition is key to lessening the sum of messages sent to the higher regions of the brain. In some lower vertebrates (e.g. the pigeon),  control of messages is "centrifugal"  – that is, one layer can control another, or higher regions of the brain can drive the retinal nerve cells, but in primates, this does not occur.<ref name="eb" />

==== Layers imagable with optical coherence tomography ====
Using [[Physics:Optical coherence tomography|optical coherence tomography]] (OCT), 18 layers can be identified in the retina. The layers and anatomical correlation are:<ref name="sciencedirect.com">{{cite journal|last1=Cuenca|first1=Nicolás|last2=Ortuño-Lizarán|first2=Isabel|last3=Pinilla|first3=Isabel|title=Cellular Characterization of OCT and Outer Retinal Bands Using Specific Immunohistochemistry Markers and Clinical Implications.|journal=Ophthalmology|date=March 2018|volume=125|issue=3|pages=407–422|doi=10.1016/j.ophtha.2017.09.016|pmid=29037595|hdl=10045/74474|url=http://rua.ua.es/dspace/bitstream/10045/74474/5/2018_Cuenca_etal_Ophthalmology_revised.pdf|hdl-access=free}}</ref><ref name=":0">{{Cite journal|last1=Staurenghi|first1=Giovanni|last2=Sadda|first2=Srinivas|last3=Chakravarthy|first3=Usha|last4=Spaide|first4=Richard F.|title=Proposed Lexicon for Anatomic Landmarks in Normal Posterior Segment Spectral-Domain Optical Coherence Tomography|journal=Ophthalmology|volume=121|issue=8|pages=1572–1578|doi=10.1016/j.ophtha.2014.02.023|pmid=24755005|year=2014}}</ref><ref>{{Cite book |author1=Meyer, Carsten H. |author2=Saxena, Sandeep |author3=Sadda, Srinivas R. |title=Spectral domain optical coherence tomography in macular diseases |date=2017 |publisher=Springer |isbn=978-8132236108 |location=New Delhi |oclc=964379175}}</ref>

[[File:Retina-OCT800.png|thumb|Time-Domain OCT of the macular area of a retina at 800 nm, axial resolution 3 μm]]
[[File:SD-OCT Macula Cross-Section.png|thumb|Spectral-Domain OCT macula cross-section scan]]
[[File:Macula Histology OCT.jpg|alt=macula histology (OCT)|thumb|Macula histology (OCT)]]
From innermost to outermost, the layers identifiable by OCT are as follows:

{| class="wikitable"
|-
!#!!OCT Layer / Conventional Label!!Anatomical Correlate
!Reflectivity
[[Physics:Optical coherence tomography|on OCT]]
!Specific
anatomical

boundaries?
!Additional
references
|-
|1
|[[Biology:Vitreous body|Posterior cortical vitreous]]
|Posterior cortical vitreous
|Hyper-reflective
|Yes
|<ref name=":0" />
|-
|''2''
|''Preretinal space''
|''In eyes where the [[Biology:Vitreous body|vitreous]] has fully or partially [[Medicine:Posterior vitreous detachment|detached]] from the retina, this is the space created between the posterior cortical vitreous face and the internal limiting membrane of the retina.''
|''Hypo-reflective''
|
|''<ref name=":0" />''
|-
| rowspan="2" |3|| [[Medicine:Internal limiting membrane|Internal limiting membrane]] (ILM) || Formed by Müller cell endfeet
''(unclear if it can be observed on OCT)''
| rowspan="2" |Hyper-reflective
| rowspan="2" |No
| rowspan="2" |<ref name=":0" />
|-
|[[Medicine:Nerve fiber layer|Nerve fiber layer]] (NFL)
|[[Biology:Ganglion cell|Ganglion cell]] axons travelling towards the [[Biology:Optic nerve|optic nerve]]
|-
|4|| [[Medicine:Ganglion cell layer|Ganglion cell layer]] (GCL) || [[Biology:Ganglion cell|Ganglion cell]] bodies (and some displaced amacrine cells)
|Hypo-reflective
|
|<ref name=":0" />
|-
|5|| [[Medicine:Inner plexiform layer|Inner plexiform layer]] (IPL) || Synapses between [[Biology:Retina bipolar cell|bipolar]], amacrine and ganglion cells
|Hyper-reflective
|
|<ref name=":0" />
|-
|6|| [[Medicine:Inner nuclear layer|Inner nuclear layer]] (INL) ||a) [[Biology:Retina horizontal cell|Horizontal]], [[Biology:Retina bipolar cell|bipolar]] and amacrine cell bodies

b) Müller cell nuclei
|Hypo-reflective
|
|<ref name=":0" />
|-
|7|| [[Medicine:Outer plexiform layer|Outer plexiform layer]] (OPL) || Synapses between [[Biology:Photoreceptor cell|photoreceptor]], [[Biology:Retina bipolar cell|bipolar]] and horizontal cells
|Hyper-reflective
|
|<ref name=":0" />
|-
| rowspan="2" |8||(Inner half) Henle's nerve fiber layer (HL)
| [[Biology:Photoreceptor cell|Photoreceptor]] axons

(obliquely orientated fibres; not present in mid-peripheral or peripheral retina)
| rowspan="2" |Hypo-reflective
| rowspan="2" |No
| rowspan="2" |<ref name=":0" />
|-
|(Outer half) [[Medicine:Outer nuclear layer|Outer nuclear layer]] (ONL)
|The [[Biology:Photoreceptor cell|photoreceptor]] cell bodies
|-
|9|| [[Medicine:External limiting membrane|External limiting membrane]] (ELM)
| Made of zonulae adherens between Müller cells and photoreceptor inner segments
|Hyper-reflective
|
|<ref name=":0" />
|-
|10|| Myoid zone (MZ) || The innermost portion of the [[Biology:Photoreceptor cell|photoreceptor inner segment (IS)]] containing:
* Smooth and rough endoplasmic reticulum
* Ribosomes
* Golgi bodies
* Microtubules
* ''(rarely: mitochondria)''
|Hypo-reflective
|No
|<ref name="Hildebrand 2011 39–65">{{Cite book|title=Pediatric Retina|last1=Hildebrand|first1=Göran Darius|last2=Fielder|first2=Alistair R.|chapter=Anatomy and Physiology of the Retina |date=2011|publisher=Springer, Berlin, Heidelberg|isbn=978-3642120404|pages=39–65|doi=10.1007/978-3-642-12041-1_2}}</ref><ref>{{Cite journal|last1=Turgut|first1=Burak|last2=University|first2=Fırat|last3=Medicine|first3=School of|last4=Ophthalmology|first4=Department of|last5=Elazig|last6=Turkey|title=Past and Present Terminology for the Retinal and Choroidal Structures in Optical Coherence Tomography|journal=European Ophthalmic Review|volume=11|issue=1|pages=59|doi=10.17925/eor.2017.11.01.59|year=2017|doi-broken-date=26 January 2024 |doi-access=free}}</ref>
|-
| rowspan="2" |11|| Ellipsoid zone (EZ) || The outermost portion of the [[Biology:Photoreceptor cell|photoreceptor inner segment (IS)]] packed with [[Biology:Mitochondria|mitochondria]]
| rowspan="2" |'''Very Hyper-reflective'''
| rowspan="2" |No
| rowspan="2" |<ref name="sciencedirect.com"/><ref>{{cite web|title=Outer Retinal Layers as Predictors of Vision Loss|url=https://www.reviewofophthalmology.com/article/outer-retinal-layers-as-predictors-of-vision-loss|website=Review of Ophthalmology}}</ref><ref name="Hildebrand 2011 39–65"/><ref name=":0"/><ref>{{cite web|title=The ABCs of OCT|url=https://www.reviewofoptometry.com/article/the-abcs-of-oct|website=Review of Optometry}}</ref><ref>{{cite journal|last1=Sherman|first1=J|title=Photoreceptor integrity line joins the nerve fiber layer as key to clinical diagnosis.|journal=Optometry|date=June 2009|volume=80|issue=6|pages=277–278|doi=10.1016/j.optm.2008.12.006|pmid=19465337}}</ref>
|-
|IS/OS junction or Photoreceptor integrity line (PIL)
|The photoreceptor [[Biology:Photoreceptor cell|connecting cilia]] which bridge the inner and outer segments of the photoreceptor cells.
|-
|12|| [[Biology:Photoreceptor cell|Photoreceptor outer segments (OS)]] || The [[Biology:Photoreceptor cell|photoreceptor outer segments (OS)]] which contain disks filled with [[Biology:Opsin|opsin]], the molecule that absorbs photons.
|Hypo-reflective
|
| rowspan="2" |<ref>{{Cite news|url=https://www.reviewofophthalmology.com/article/outer-retinal-layers-as-predictors-of-vision-loss|title=Outer Retinal Layers as Predictors of Vision Loss|last=Boston|first=Marco A. Bonini Filho, MD, and Andre J. Witkin, MD|access-date=7 April 2018}}</ref><ref name=":0" />
|-
|-
|13|| Interdigitation zone (IZ) || Apices of the [[Medicine:Retinal pigment epithelium|RPE]] cells which encase part of the cone OSs. 
''Poorly distinguishable from RPE.'' ''Previously: "cone outer segment tips line"'' ''(COST)''
|Hyper-reflective
|No
|-
  | rowspan="3" | 14
  | rowspan="3" | [[Medicine:Retinal pigment epithelium|RPE]]/Bruch's complex
  | [[Medicine:Retinal pigment epithelium|RPE]] phagosome zone
  | '''Very Hyper-reflective'''
  | rowspan="3" | No
  | rowspan="3" | <ref name="sciencedirect.com"/><ref name=":0" />
|-
  | [[Medicine:Retinal pigment epithelium|RPE]] melanosome zone
  | Hypo-reflective
|-
  | [[Medicine:Retinal pigment epithelium|RPE]] mitochondria zone + Junction between the RPE & [[Medicine:Bruch's membrane|Bruch's membrane]]
  | '''Very Hyper-reflective'''
|-
|15
|Choriocapillaris
| colspan="2" |Thin layer of moderate reflectivity in inner choroid
|No
|<ref name=":0" />
|-
|16
|[[Medicine:Sattler's layer|Sattler's layer]]
| colspan="2" |Thick layer of round or ovalshaped hyperreflective profiles, with hyporeflective cores in mid-choroid
|
|<ref name=":0" />
|-
|17
|Haller's layer
| colspan="2" |Thick layer of oval-shaped hyperreflective profiles, with hyporeflective cores in outer choroid
|
|<ref name=":0" />
|-
|18
|Choroidal-scleral juncture
| colspan="2" |Zone at the outer choroid with a marked change in texture, in which large circular or ovoid profiles abut a
homogenous region of variable reflectivity
|
|<ref name=":0" />
|}

=== Development ===
Retinal development begins with the establishment of the eye fields mediated by the [[Biology:Sonic hedgehog|SHH]] and [[Biology:SIX3|SIX3]] proteins, with subsequent development of the optic vesicles regulated by the [[Biology:PAX6|PAX6]] and LHX2 proteins.<ref name="Heavner">{{cite journal |last = Heavner |first = W |author2 = Pevny, L |title = Eye development and retinogenesis. |journal = Cold Spring Harbor Perspectives in Biology |date = 1 December 2012 |volume = 4 |issue = 12 |pmid = 23071378 |doi = 10.1101/cshperspect.a008391 |pages = a008391 |pmc = 3504437 }}</ref> The role of Pax6 in eye development was elegantly demonstrated by Walter Gehring and colleagues, who showed that ectopic expression of Pax6 can lead to eye formation on [[Biology:Drosophila|Drosophila]] antennae, wings, and legs.<ref>{{cite journal |last = Halder |first = G |author2 = Callaerts, P |author3 = Gehring, WJ |title = Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila |journal = Science |date = 24 March 1995 |volume = 267 |issue = 5205 |pages = 1788–1792 |pmid = 7892602 |doi = 10.1126/science.7892602 |bibcode = 1995Sci...267.1788H }}</ref> The optic vesicle gives rise to three structures: the neural retina, the retinal pigmented epithelium, and the optic stalk. The neural retina contains the retinal progenitor cells (RPCs) that give rise to the seven cell types of the retina. Differentiation begins with the [[Biology:Retinal ganglion cell|retinal ganglion cell]]s and concludes with production of the Muller glia.<ref>{{Cite journal|last=Cepko|first=Connie|date=September 2014|title=Intrinsically different retinal progenitor cells produce specific types of progeny|journal=Nature Reviews Neuroscience|volume=15|issue=9|pages=615–627|doi=10.1038/nrn3767|pmid=25096185|s2cid=15038502|issn=1471-003X}}</ref> Although each cell type differentiates from the RPCs in a sequential order, there is considerable overlap in the timing of when individual cell types differentiate.<ref name="Heavner" /> The cues that determine a RPC daughter cell fate are coded by multiple transcription factor families including the [[Biology:Basic helix-loop-helix|bHLH]] and [[Biology:Homeobox|homeodomain]] factors.<ref>{{cite journal |last = Hatakeyama |first = J |author2 = Kageyama, R |title = Retinal cell fate determination and bHLH factors |journal = Seminars in Cell & Developmental Biology |date = February 2004 |volume = 15 |issue = 1 |pages = 83–89 |pmid = 15036211 |doi = 10.1016/j.semcdb.2003.09.005 }}</ref><ref name=":1">{{Cite journal|last1=Lo Giudice|first1=Quentin|last2=Leleu|first2=Marion|last3=La Manno|first3=Gioele|last4=Fabre|first4=Pierre J.|date=1 September 2019|title=Single-cell transcriptional logic of cell-fate specification and axon guidance in early-born retinal neurons|journal=Development|volume=146|issue=17|pages=dev178103|doi=10.1242/dev.178103|pmid=31399471|issn=0950-1991|doi-access=free}}</ref>

In addition to guiding cell fate determination, cues exist in the retina to determine the dorsal-ventral (D-V) and nasal-temporal (N-T) axes. The D-V axis is established by a ventral to dorsal gradient of [[Biology:VAX1|VAX2]], whereas the N-T axis is coordinated by expression of the forkhead transcription factors FOXD1 and [[Biology:FOXG1|FOXG1]]. Additional gradients are formed within the retina.<ref name=":1" /> This spatial distribution may aid in proper targeting of RGC axons that function to establish the retinotopic map.<ref name="Heavner" />

=== Blood supply ===
{{Multiple issues|
{{Self-published|section|date=October 2016}}
}}

[[File:Fundus photograph of normal right eye.jpg|thumb|left|Fundus photograph showing the blood vessels in a normal human retina. Veins are darker and slightly wider than corresponding arteries. The optic disc is at right, and the macula lutea is near the centre.]]

The retina is stratified into distinct layers, each containing specific cell types or cellular compartments<ref>{{Cite book |title = Clinical anatomy and physiology of the visual system |last = Remington|first = Lee Ann|date = 2012 |publisher = Elsevier/Butterworth-Heinemann |isbn = 978-1-4377-1926-0 |edition = 3rd |location = St. Louis |oclc = 745905738 }}</ref> that have metabolisms with different nutritional requirements.<ref>{{cite journal |last1 = Yu |first1 = DY |last2 = Yu |first2 = PK |last3 = Cringle |first3 = SJ |last4 = Kang |first4 = MH |last5 = Su |first5 = EN |title = Functional and morphological characteristics of the retinal and choroidal vasculature. |journal = Progress in Retinal and Eye Research |date = May 2014 |volume = 40 |pages = 53–93 |doi = 10.1016/j.preteyeres.2014.02.001 |pmid = 24583621 |s2cid = 21312546 }}</ref> To satisfy these requirements, the ophthalmic artery bifurcates and supplies the retina via two distinct vascular networks: the choroidal network, which supplies the choroid and the outer retina, and the retinal network, which supplies the retina's inner layer.<ref>{{cite book |last1 = Kiel |first1 = Jeffrey W. |title = Anatomy |publisher = Morgan & Claypool Life Sciences |url = https://www.ncbi.nlm.nih.gov/books/NBK53329/ |access-date = 17 April 2017 |url-status = live |archive-url = https://web.archive.org/web/20171205073518/https://www.ncbi.nlm.nih.gov/books/NBK53329/ |archive-date = 5 December 2017 }}</ref>

Although the inverted retina of vertebrates appears counter-intuitive, it is necessary for the proper functioning of the retina. The photoreceptor layer must be embedded in the retinal pigment epithelium (RPE), which performs at least seven vital functions,<ref>{{cite web|last1=Strauss|first1=Olaf|title=The retinal pigment epithelium|url=http://webvision.med.utah.edu/book/part-ii-anatomy-and-physiology-of-the-retina/the-retinal-pigment-epithelium|website=Webvision|access-date=1 January 2018}}</ref> one of the most obvious being to supply oxygen and other necessary nutrients needed for the photoreceptors to function. 

====Energy requirements====
The energy requirements of the retina are even greater than that of the brain.<ref name="Viegas Neuhauss"></ref>  This is due to the additional energy needed to continuously renew the photoreceptor outer segments, of which 10% are shed daily.<ref name="Viegas Neuhauss"></ref> Energy demands are greatest during dark adaptation when its sensitivity is most enhanced.<ref name="Kaynezhad Tachtsidis Sivaprasad Jeffery">{{cite journal | last1=Kaynezhad | first1=Pardis | last2=Tachtsidis | first2=Ilias | last3=Sivaprasad | first3=Sobha | last4=Jeffery | first4=Glen | title=Watching the human retina breath in real time and the slowing of mitochondrial respiration with age | journal=Scientific Reports | volume=13 | issue=1 | date=2023 | issn=2045-2322 | doi=10.1038/s41598-023-32897-7 | page=6445| pmid=37081065 | pmc=10119193 | bibcode=2023NatSR..13.6445K }}</ref> The choroid supplies about 75% of these nutrients to the retina and the retinal vasculature only 25%.<ref name="Kolb">{{cite journal|last1=Kolb|first1=Helga|title=Simple Anatomy of the Retina|url=http://webvision.med.utah.edu/book/part-i-foundations/simple-anatomy-of-the-retina/|website=Webvision|year=1995|pmid=21413391|access-date=1 January 2018}}</ref>

When light strikes 11-cis-retinal (in the disks in the rods and cones), 11-cis-retinal changes to all-trans-retinal which then triggers changes in the opsins. Now, the outer segments do not regenerate the retinal back into the cis- form once it has been changed by light. Instead the retinal is pumped out to the surrounding RPE where it is regenerated and transported back into the outer segments of the photoreceptors. This recycling function of the RPE protects the photoreceptors against photo-oxidative damage<ref>{{Cite web|title=LIGHT-INDUCED DAMAGE to the RETINA|url=http://photobiology.info/Rozanowska.html|access-date=2023-02-23|website=photobiology.info}}</ref><ref>{{cite web |title=Diagrammatic representation of disc shedding and phagosome retrieval into the pigment epithelial cell |url=http://webvision.med.utah.edu/imageswv/photphag.jpeg |url-status=live |archive-url=https://web.archive.org/web/20120921011139/http://webvision.med.utah.edu/imageswv/photphag.jpeg |archive-date=21 September 2012 |access-date=22 April 2022}}</ref> and allows the photoreceptor cells to have decades-long useful lives.

==== In birds ====
The bird retina is devoid of blood vessels, perhaps to give unobscured passage of light for forming images, thus giving better resolution. It is, therefore, a considered view that the bird retina depends for nutrition and oxygen supply on a specialized organ, called the "pecten" or [[Biology:Pecten oculi|pecten oculi]], located on the blind spot or optic disk. This organ is extremely rich in blood vessels and is thought to supply nutrition and oxygen to the bird retina by diffusion through the vitreous body. The pecten is highly rich in alkaline phosphatase activity and polarized cells in its bridge portion – both befitting its secretory role.<ref>{{cite journal |author1 = Bawa S.R. |author2 = YashRoy R.C. |year = 1972 |title = Effect of dark and light adaptation on the retina and pecten of chicken |url = https://www.researchgate.net/publication/18108932 |journal = Experimental Eye Research |volume = 13 |issue = 1 |pages = 92–97 |doi = 10.1016/0014-4835(72)90129-7 |pmid = 5060117 |url-status = live |archive-url = https://web.archive.org/web/20141009111444/http://www.researchgate.net/publication/18108932_Effect_of_dark_and_light_adaptation_on_the_retina_and_pecten_of_chicken?ev=prf_pub |archive-date = 9 October 2014 }}</ref> Pecten cells are packed with dark melanin granules, which have been theorized to keep this organ warm with the absorption of stray light falling on the pecten. This is considered to enhance metabolic rate of the pecten, thereby exporting more nutritive molecules to meet the stringent energy requirements of the retina during long periods of exposure to light.<ref>{{cite journal |last1 = Bawa |first1 = S.R. |last2 = YashRoy |first2 = R.C. |year = 1974 |title = Structure and function of vulture pecten |url = https://www.researchgate.net/publication/231569868 |journal = Cells Tissues Organs |volume = 89 |issue = 3 |pages = 473–480 |doi = 10.1159/000144308 |pmid = 4428954 |url-status = live |archive-url = https://web.archive.org/web/20150714070339/http://www.researchgate.net/publication/231569868_Structure_and_function_of_vulture_pecten?ev=prf_pub |archive-date = 14 July 2015 }}</ref>

=== Biometric identification and diagnosis of disease ===

The bifurcations and other physical characteristics of the inner retinal vascular network are known to vary among individuals,<ref name="Sherman81">{{cite journal |last1 = Sherman |first1 = T |year = 1981 |title = On connecting large vessels to small – the meaning of murray law |journal = Journal of General Physiology |volume = 78 |issue = 4 |pages = 431–453 |doi = 10.1085/jgp.78.4.431 |pmid = 7288393 |pmc = 2228620 }}</ref> and these individual variances have been used for [[Biology:Retinal scan|biometric identification]] and for early detection of the onset of disease. The mapping of vascular bifurcations is one of the basic steps in biometric identification.<ref name="Azzopardi2011">{{cite book |author1 = Azzopardi G. |author2 = Petkov N. |title = Computer Analysis of Images and Patterns |chapter = Detection of Retinal Vascular Bifurcations by Trainable V4-Like Filters |year = 2011 |url = http://www.cs.rug.nl/~petkov/publications/2011caip_bifurcations.pdf |volume = 6854 |pages = 451–459 |doi = 10.1007/978-3-642-23672-3_55 |series = Lecture Notes in Computer Science |isbn = 978-3-642-23671-6 |url-status = live |archive-url = https://web.archive.org/web/20170809091954/http://www.cs.rug.nl/~petkov/publications/2011caip_bifurcations.pdf |archive-date = 9 August 2017 }}</ref> Results of such analyses of retinal blood vessel structure can be evaluated against the ground truth data<ref>{{cite web |title=Retinal fundus images – Ground truth of vascular bifurcations and crossovers|url=http://www.cs.rug.nl/~imaging/databases/retina_database/retinalfeatures_database.html |website=[[Organization:University of Groningen|University of Groningen]] |access-date=20 April 2018}}</ref> of vascular bifurcations of retinal fundus images that are obtained from the DRIVE dataset.<ref>{{cite web |title=DRIVE: Digital Retinal Images for Vessel Extraction |url=http://www.isi.uu.nl/Research/Databases/DRIVE/ |website=Image Sciences Institute, [[Organization:Utrecht University|Utrecht University]] |access-date=20 April 2018 |archive-date=6 August 2020 |archive-url=https://web.archive.org/web/20200806153015/http://www.isi.uu.nl/Research/Databases/DRIVE/ |url-status=dead }}</ref> In addition, the classes of vessels of the DRIVE dataset have also been identified,<ref name="Qureshi2013">{{Cite book |last1 = Qureshi |first1 = T. A. |last2 = Habib |first2 = M. |last3 = Hunter |first3 = A. |last4 = Al-Diri |first4 = B. |title = Proceedings of the 26th IEEE International Symposium on Computer-Based Medical Systems |chapter = A manually-labeled, artery/Vein classified benchmark for the DRIVE dataset |date = June 2013 |pages = 485–488 |doi = 10.1109/cbms.2013.6627847 |isbn = 978-1-4799-1053-3 |s2cid = 7705121 }}</ref> and an automated method for accurate extraction of these bifurcations is also available.<ref name="Qureshi2014">{{Cite book |last1 = Qureshi |first1 = T. A. |last2 = Hunter |first2 = A. |last3 = Al-Diri |first3 = B. |title = 2014 IEEE Conference on Computer Vision and Pattern Recognition |chapter = A Bayesian Framework for the Local Configuration of Retinal Junctions |date = June 2014 |pages = 3105–3110 |doi = 10.1109/cvpr.2014.397 |isbn = 978-1-4799-5118-5 |citeseerx = 10.1.1.1026.949 |s2cid = 14654500 }}</ref> Changes in retinal blood circulation are seen with aging<ref>{{cite journal |vauthors = Adar SD, Klein R, Klein BE, Szpiro AA, Cotch MF, Wong TY, etal |year = 2010 |title = Air Pollution and the microvasculature: a crosssectional assessment of in vivo retinal images in the population based multiethnic study of atherosclerosis (MESA) |journal = PLOS Med |volume = 7 |issue = 11 |page = e1000372 |doi = 10.1371/journal.pmed.1000372 |pmid = 21152417 |pmc = 2994677 |doi-access = free }}</ref> and exposure to air pollution,<ref name="Louwies">{{Cite journal |last1 = Louwies |first1 = Tijs |last2 = Panis |first2 = Luc Int |last3 = Kicinski |first3 = Michal |last4 = Boever |first4 = Patrick De |last5 = Nawrot |first5 = Tim S. |year = 2013 |title = Retinal Microvascular Responses to Short-Term Changes in Particulate Air Pollution in Healthy Adults |journal = Environmental Health Perspectives |volume = 121 |issue = 9 |pages = 1011–1016 |doi = 10.1289/ehp.1205721 |pmc = 3764070 |pmid = 23777785 }}</ref> and may indicate cardiovascular diseases such as hypertension and atherosclerosis.<ref>{{Cite journal |last1 = Tso |first1 = Mark O.M. |last2 = Jampol |first2 = Lee M. |title = Pathophysiology of Hypertensive Retinopathy |journal = Ophthalmology |volume = 89 |issue = 10 |pages = 1132–1145 |doi = 10.1016/s0161-6420(82)34663-1 |pmid = 7155524 |year = 1982 }}</ref><ref name="Chapman2002">{{Cite journal |last1 = Chapman |first1 = N. |last2 = Dell'omo |first2 = G. |last3 = Sartini |first3 = M. S. |last4 = Witt |first4 = N. |last5 = Hughes |first5 = A. |last6 = Thom |first6 = S. |last7 = Pedrinelli |first7 = R. |date = 1 August 2002 |title = Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina |journal = Clinical Science |volume = 103 |issue = 2 |pages = 111–116 |doi = 10.1042/cs1030111 |issn = 0143-5221 |pmid = 12149100 }}</ref><ref name="Patton06">{{cite journal |last1 = Patton |first1 = N. |last2 = Aslam |first2 = T. |last3 = MacGillivray |first3 = T. |last4 = Deary |first4 = I. |last5 = Dhillon |first5 = B. |last6 = Eikelboom |first6 = R. |last7 = Yogesan |first7 = K. |last8 = Constable |first8 = I. |year = 2006 |title = Retinal image analysis: Concepts, applications and potential |journal = Progress in Retinal and Eye Research |volume = 25 |issue = 1 |pages = 99–127 |doi = 10.1016/j.preteyeres.2005.07.001 |pmid = 16154379 |s2cid = 7434103 }}</ref> Determining the equivalent width of arterioles and venules near the optic disc is also a widely used technique to identify cardiovascular risks.<ref>{{cite journal |vauthors = Wong TY, Knudtson MD, Klein R, Klein BE, Meuer SM, Hubbard LD |year = 2004 |title = Computer assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: methodology, correlation between eyes, and effect of refractive errors |journal = Ophthalmology |volume = 111 |issue = 6 |pages = 1183–1190 |doi = 10.1016/j.ophtha.2003.09.039 |pmid = 15177969 }}</ref>

== Function ==

The retina translates an optical image into neural impulses starting with the patterned excitation of the colour-sensitive pigments of its rods and cones, the retina's [[Biology:Photoreceptor cell|photoreceptor cell]]s. The excitation is processed by the neural system and various parts of the brain working in parallel to form a representation of the external environment in the brain.

The cones respond to bright light and mediate high-resolution colour vision during daylight illumination (also called [[Biology:Photopic vision|photopic vision]]). The rod responses are saturated at daylight levels and do not contribute to pattern vision. However, rods do respond to dim light and mediate lower-resolution, monochromatic vision under very low levels of illumination (called [[Biology:Scotopic vision|scotopic vision]]). The illumination in most office settings falls between these two levels and is called [[Biology:Mesopic vision|mesopic vision]]. At mesopic light levels, both the rods and cones are actively contributing pattern information. What contribution the rod information makes to pattern vision under these circumstances is unclear.

The response of cones to various wavelengths of light is called their spectral sensitivity. In normal human vision, the spectral sensitivity of a cone falls into one of three subtypes, often called blue, green, and red, but more accurately known as short, medium, and long wavelength-sensitive cone subtypes. It is a lack of one or more of the cone subtypes that causes individuals to have deficiencies in colour vision or various kinds of colour blindness. These individuals are not blind to objects of a particular colour, but are unable to distinguish between colours that can be distinguished by people with normal vision. Humans have this trichromatic vision, while most other mammals lack cones with red sensitive pigment and therefore have poorer dichromatic colour vision. However, some animals have four spectral subtypes, e.g. the trout adds an ultraviolet subgroup to short, medium, and long subtypes that are similar to humans. Some fish are sensitive to the polarization of light as well.

In the photoreceptors, exposure to light hyperpolarizes the membrane in a series of graded shifts. The outer cell segment contains a [[Biology:Photopigment|photopigment]]. Inside the cell the normal levels of [[Chemistry:Cyclic guanosine monophosphate|cyclic guanosine monophosphate]] (cGMP) keep the Na+ channel open, and thus in the resting state the cell is depolarised. The [[Physics:Photon|photon]] causes the [[Chemistry:Retinal|retinal]] bound to the receptor protein to isomerise to [[Chemistry:Retinal|trans-retinal]]. This causes the receptor to activate multiple G-proteins. This in turn causes the Ga-subunit of the protein to activate a phosphodiesterase (PDE6), which degrades cGMP, resulting in the closing of Na+ cyclic nucleotide-gated ion channels (CNGs). Thus the cell is hyperpolarised. The amount of neurotransmitter released is reduced in bright light and increases as light levels fall. The actual photopigment is bleached away in bright light and only replaced as a chemical process, so in a transition from bright light to darkness the eye can take up to thirty minutes to reach full sensitivity.

When thus excited by light, the photoceptor sends a proportional response [[Biology:Synapse|synaptically]] to bipolar cells which in turn signal the [[Biology:Retinal ganglion cell|retinal ganglion cell]]s. The photoreceptors are also cross-linked by horizontal cells and [[Biology:Amacrine cell|amacrine cell]]s, which modify the synaptic signal before it reaches the ganglion cells, the neural signals being intermixed and combined. Of the retina's nerve cells, only the retinal ganglion cells and few amacrine cells create [[Biology:Action potential|action potential]]s.

In the retinal ganglion cells there are two types of response, depending on the [[Biology:Receptive field|receptive field]] of the cell. The receptive fields of retinal ganglion cells comprise a central, approximately circular area, where light has one effect on the firing of the cell, and an annular surround, where light has the opposite effect. In ON cells, an increment in light intensity in the centre of the receptive field causes the firing rate to increase. In OFF cells, it makes it decrease. In a linear model, this response profile is well described by a [[Difference of Gaussians|difference of Gaussians]] and is the basis for [[Edge detection|edge detection]] algorithms. Beyond this simple difference, ganglion cells are also differentiated by chromatic sensitivity and the type of spatial summation. Cells showing linear spatial summation are termed X cells (also called parvocellular, P, or midget ganglion cells), and those showing non-linear summation are Y cells (also called magnocellular, M, or parasol retinal ganglion cells), although the correspondence between X and Y cells (in the cat retina) and P and M cells (in the primate retina) is not as simple as it once seemed.

In the transfer of visual signals to the brain, the visual pathway, the retina is vertically divided in two, a temporal (nearer to the temple) half and a nasal (nearer to the nose) half. The axons from the nasal half cross the brain at the optic chiasma to join with axons from the temporal half of the other eye before passing into the lateral geniculate body.

Although there are more than 130 million retinal receptors, there are only approximately 1.2 million fibres (axons) in the optic nerve. So, a large amount of pre-processing is performed within the retina. The [[Medicine:Fovea centralis|fovea]] produces the most accurate information. Despite occupying about 0.01% of the visual field (less than 2° of [[Visual angle|visual angle]]), about 10% of axons in the optic nerve are devoted to the fovea. The resolution limit of the fovea has been determined to be around 10,000 points. The information capacity is estimated at 500,000 bits per second (for more information on bits, see [[Information theory|information theory]]) without colour or around 600,000 bits per second including colour.<ref>{{Cite book |author1=Chen, Janglin |author2=Cranton, Wayne |author3=Fihn, Mark |title=Handbook of visual display technology |edition=2nd |date=2016 |location=Cham, Switzerland |publisher=Springer |isbn=9783319143460 |oclc=962009228}}</ref>

=== Spatial encoding ===
[[File:Receptive field.png|thumb|upright=1.36|right|On-centres and off-centres of the retina]]

When the retina sends neural impulses representing an image to the brain, it spatially encodes (compresses) those impulses to fit the limited capacity of the optic nerve. Compression is necessary because there are 100 times more [[Biology:Photoreceptor cell|photoreceptor cell]]s than [[Biology:Ganglion cell|ganglion cell]]s. This is done by "[[Decorrelation|decorrelation]]", which is carried out by the "centre–surround structures", which are implemented by the bipolar and ganglion cells.

There are two types of centre–surround structures in the retina – on-centres and off-centres. On-centres have a positively weighted centre and a negatively weighted surround. Off-centres are just the opposite. Positive weighting is more commonly known as [[Biology:Chemical synapse#Receptor binding|excitatory]], and negative weighting as [[Biology:Chemical synapse#Receptor binding|inhibitory]].

These centre–surround structures are not physical apparent, in the sense that one cannot see them by staining samples of tissue and examining the retina's anatomy. The centre–surround structures are logical (i.e., mathematically abstract) in the sense that they depend on the connection strengths between bipolar and ganglion cells. It is believed that the connection strength between cells is caused by the number and types of [[Biology:Ion channel|ion channel]]s embedded in the [[Biology:Synapse|synapse]]s between the bipolar and ganglion cells.

The centre–surround structures are mathematically equivalent to the [[Edge detection|edge detection]] algorithms used by computer programmers to extract or enhance the edges in a digital photograph. Thus, the retina performs operations on the image-representing impulses to enhance the edges of objects within its visual field. For example, in a picture of a dog, a cat and a car, it is the edges of these objects that contain the most information. In order for higher functions in the brain (or in a computer for that matter) to extract and classify objects such as a dog and a cat, the retina is the first step to separating out the various objects within the scene.

As an example, the following [[Matrix (mathematics)|matrix]] is at the heart of a computer [[Algorithm|algorithm]] that implements edge detection. This matrix is the computer equivalent to the centre–surround structure. In this example, each box (element) within this matrix would be connected to one photoreceptor. The photoreceptor in the centre is the current receptor being processed. The centre photoreceptor is multiplied by the +1 weight factor. The surrounding photoreceptors are the "nearest neighbors" to the centre and are multiplied by the −1/8 value. The sum of all nine of these elements is finally calculated. This summation is repeated for every photoreceptor in the image by shifting left to the end of a row and then down to the next line.

{| class="wikitable"
|-
| style="background:lightyellow;" | -1/8|| style="background:lightyellow;" |-1/8|| style="background:lightyellow;" |-1/8
|-
| style="background:lightyellow;" | -1/8|| style="background:lightblue;" |+1|| style="background:lightyellow;" |-1/8
|-
| style="background:lightyellow;" | -1/8|| style="background:lightyellow;" |-1/8|| style="background:lightyellow;" |-1/8
|}

The total sum of this matrix is zero, if all the inputs from the nine photoreceptors are of the same value. The zero result indicates the image was uniform (non-changing) within this small patch. Negative or positive sums mean the image was varying (changing) within this small patch of nine photoreceptors.

The above matrix is only an approximation to what really happens inside the retina. The differences are:
* The above example is called "balanced". The term balanced means that the sum of the negative weights is equal to the sum of the positive weights so that they cancel out perfectly. Retinal ganglion cells are almost never perfectly balanced.
* The table is square while the centre–surround structures in the retina are circular.
* Neurons operate on spike trains traveling down nerve cell axons. Computers operate on a single [[Floating-point arithmetic|floating-point number]] that is essentially constant from each input [[Pixel|pixel]]. (The computer pixel is basically the equivalent of a biological photoreceptor.)
* The retina performs all these calculations in parallel while the computer operates on each pixel one at a time. The retina performs no repeated summations and shifting as would a computer.
* Finally, the horizontal and [[Biology:Amacrine cell|amacrine cell]]s play a significant role in this process, but that is not represented here.

Here is an example of an input image and how edge detection would modify it.

[[File:Edge-detection-2.jpg|frameless|upright=2.5|alt=input image]]

Once the image is spatially encoded by the centre–surround structures, the signal is sent out along the optic nerve (via the axons of the ganglion cells) through the [[Biology:Optic chiasm|optic chiasm]] to the LGN ([[Biology:Lateral geniculate nucleus|lateral geniculate nucleus]]). The exact function of the LGN is unknown at this time. The output of the LGN is then sent to the back of the brain. Specifically, the output of the LGN "radiates" out to the V1 primary visual cortex.

Simplified signal flow: Photoreceptors → Bipolar → Ganglion → Chiasm → LGN → V1 cortex

[[File:ERP - optic cabling.jpg|frameless|upright=2.273|alt=ERP optic cabling]]

== Clinical significance{{anchor|Diseases_and_disorders}} ==
There are many inherited and acquired diseases or disorders that may affect the retina. Some of them include:
* [[Medicine:Retinitis pigmentosa|Retinitis pigmentosa]] is a group of genetic diseases that affect the retina and cause the loss of night vision and peripheral vision.
* [[Medicine:Macular degeneration|Macular degeneration]] describes a group of diseases characterized by loss of central vision because of death or impairment of the cells in the [[Medicine:Macula|macula]].
* Cone-rod dystrophy (CORD) describes a number of diseases where vision loss is caused by deterioration of the [[Biology:Cone cell|cones]] and/or [[Biology:Rod cell|rods]] in the retina.
* In retinal separation, the retina detaches from the back of the eyeball. Ignipuncture is an outdated treatment method. The term [[Medicine:Retinal detachment|retinal detachment]] is used to describe a separation of the neurosensory retina from the [[Medicine:Retinal pigment epithelium|retinal pigment epithelium]].<ref name="Retina">{{Cite book |title = Retina |date = 2006 |publisher = Elsevier/Mosby |isbn = 978-0-323-02598-0 |edition = 4th |location = Philadelphia |pages = 2013–2015 |oclc = 62034580 }}</ref> There are several modern treatment methods for fixing a retinal detachment: pneumatic retinopexy, scleral buckle, [[Unsolved:Cryotherapy|cryotherapy]], laser photocoagulation and pars plana [[Medicine:Vitrectomy|vitrectomy]].
* Both [[Medicine:Hypertension|hypertension]] and [[Medicine:Diabetes mellitus|diabetes mellitus]] can cause damage to the tiny blood vessels that supply the retina, leading to [[Medicine:Hypertensive retinopathy|hypertensive retinopathy]] and [[Medicine:Diabetic retinopathy|diabetic retinopathy]].
* [[Medicine:Retinoblastoma|Retinoblastoma]] is a [[Medicine:Cancer|cancer]] of the retina.
* Retinal diseases in [[Biology:Dog|dog]]s include [[Medicine:Retinal dysplasia|retinal dysplasia]], [[Medicine:Progressive retinal atrophy|progressive retinal atrophy]], and sudden acquired retinal degeneration.
* ''[[Medicine:Lipaemia retinalis|Lipaemia retinalis]]'' is a white appearance of the retina, and can occur by lipid deposition in [[Medicine:Lipoprotein lipase deficiency|lipoprotein lipase deficiency]].
* ''Retinal Detachment''. The neural retina occasionally detaches from the pigment epithelium. In some instances, the cause of such detachment is injury to the eyeball that allows fluid or blood to collect between the neural retina and the pigment epithelium. Detachment is occasionally caused by contracture of fine collagenous fibrils in the vitreous humor, which pull areas of the retina toward the interior of the globe.<ref name="ReferenceA"/>
* ''Night blindness'': Night blindness occurs in any person with severe vitamin A deficiency. The reason for this is that without vitamin A, the amounts of retinal and rhodopsin that can be formed are severely depressed. This condition is called night blindness because the amount of light available at night is too little to permit adequate vision in vitamin A–deficient persons.<ref name="Guyton and Hall Physiology"/>

In addition, the retina has been described as a "window" into the brain and body, given that abnormalities detected through an examination of the retina can discover both neurological and systemic diseases.<ref>{{Cite journal|last1=Frith|first1=Peggy|last2=Mehta|first2=Arpan R|date=November 2021|title=The retina as a window into the brain|journal=The Lancet Neurology|language=en|volume=20|issue=11|pages=892|doi=10.1016/S1474-4422(21)00332-X|pmid=34687632|pmc=7611980}}</ref>

=== Diagnosis ===
A number of different instruments are available for the diagnosis of diseases and disorders affecting the retina. [[Physics:Ophthalmoscopy|Ophthalmoscopy]] and [[Engineering:Fundus photography|fundus photography]] have long been used to examine the retina. Recently, [[Astronomy:Adaptive optics|adaptive optics]] has been used to image individual rods and cones in the living human retina, and a company based in Scotland has engineered technology that allows physicians to observe the complete retina without any discomfort to patients.<ref>[http://www.ingenia.org.uk/ingenia/articles.aspx?Index=414 Seeing into the Future] {{Webarchive|url=https://web.archive.org/web/20120212190557/http://www.ingenia.org.uk/ingenia/articles.aspx?Index=414 |date=12 February 2012 }} ''Ingenia'', March 2007</ref>

The [[Medicine:Electroretinography|electroretinogram]] is used to non-invasively measure the retina's electrical activity, which is affected by certain diseases. A relatively new technology, now becoming widely available, is [[Physics:Optical coherence tomography|optical coherence tomography]] (OCT). This non-invasive technique allows one to obtain a [[Physics:Dimension|3D]] volumetric or high resolution cross-sectional tomogram of the fine structures of the retina, with histologic quality. [[Medicine:Retinal vessel analysis|Retinal vessel analysis]] is a non-invasive method to examine the small arteries and veins in the retina which allows to draw conclusions about the morphology and the function of small vessels elsewhere in the human body. It has been established as a predictor of [[Medicine:Cardiovascular disease|cardiovascular disease]]<ref>{{cite journal |last=Seidelmann |first=SB |display-authors=0 |title=Retinal Vessel Calibers in Predicting Long-Term Cardiovascular Outcomes |date=1 November 2016 |journal=Circulation |volume=134 |issue=18 |pages=1328–1338 |doi=10.1161/CIRCULATIONAHA.116.023425|pmid=27682886 |pmc=5219936 }}</ref> and seems to have, according to a study published in 2019, potential in the early detection of Alzheimer's disease.<ref>{{cite journal |last=Querques |first=G |display-authors=0 |title=Functional and morphological changes of the retinal vessels in Alzheimer's disease and mild cognitive impairment |date=11 January 2019 |journal=Scientific Reports |volume=9 |pages=63 |number=63 |doi=10.1038/s41598-018-37271-6|pmid=30635610 |pmc=6329813 |bibcode=2019NatSR...9...63Q }}</ref>

=== Treatment ===
Treatment depends upon the nature of the disease or disorder.

==== Common treatment modalities ====
The following are commonly modalities of management for retinal disease:
* Intravitreal medication, such as [[Biology:Anti–vascular endothelial growth factor therapy|anti-VEGF]] or [[Biology:Corticosteroid|corticosteroid]] agents
* Vitreoretinal surgery
* Use of nutritional supplements
* Modification of systemic risk factors for retinal disease

==== Uncommon treatment modalities ====
'''Retinal gene therapy'''

[[Biology:Gene therapy|Gene therapy]] holds promise as a potential avenue to cure a wide range of retinal diseases. This involves using a non-infectious virus to shuttle a gene into a part of the retina. Recombinant [[Biology:Adeno-associated virus|adeno-associated virus]] (rAAV) vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner.<ref>{{cite journal |author1 = Dinculescu Astra |author2 = Glushakova Lyudmyla |author3 = Seok-Hong Min |author4 = Hauswirth William W |year = 2005 |title = Adeno-associated virus-vectored gene therapy for retinal disease |journal = Human Gene Therapy |volume = 16 |issue = 6 |pages = 649–663 |doi = 10.1089/hum.2005.16.649 |pmid = 15960597 }}</ref> rAAV vectors are increasingly utilized for their ability to mediate efficient transduction of [[Medicine:Retinal pigment epithelium|retinal pigment epithelium]] (RPE), photoreceptor cells and retinal ganglion cells. Each cell type can be specifically targeted by choosing the appropriate combination of AAV [[Biology:Serotype|serotype]], promoter, and intraocular injection site.

Several clinical trials have already reported positive results using rAAV to treat [[Medicine:Leber's congenital amaurosis|Leber's congenital amaurosis]], showing that the therapy was both safe and effective.<ref name="Cideciyan 2009">{{cite journal |author1 = Cideciyan A. V. |author2 = Hauswirth W. W. |author3 = Aleman T. S. |author4 = Kaushal S. |author5 = Schwartz S. B. |author6 = Boye S. L. |author7 = Windsor E. A. M. |year = 2009 |title = Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year |journal = Human Gene Therapy |volume = 20 |issue = 9 |pages = 999–1004 |doi = 10.1089/hum.2009.086 |pmid = 19583479 |pmc = 2829287 |display-authors = etal }}</ref><ref name="Simonelli 2010">{{cite journal |author1 = Simonelli F. |author2 = Maguire A. M. |author3 = Testa F. |author4 = Pierce E. A. |author5 = Mingozzi F. |author6 = Bennicelli J. L. |author7 = Rossi S. |year = 2010 |title = Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration |journal = Molecular Therapy |volume = 18 |issue = 3 |pages = 643–650 |doi = 10.1038/mt.2009.277 |pmid = 19953081 |pmc = 2839440 |display-authors = etal }}</ref> There were no serious adverse events, and patients in all three studies showed improvement in their visual function as measured by a number of methods. The methods used varied among the three trials, but included both functional methods such as visual acuity<ref name="Simonelli 2010" /><ref name="Maguire 2008">{{cite journal |author1 = Maguire A. M. |author2 = Simonelli F. |author3 = Pierce E. A. |author4 = Pugh E. N. |author5 = Mingozzi F. |author6 = Bennicelli J. |author7 = Banfi S. |year = 2008 |title = Safety and efficacy of gene transfer for Leber's congenital amaurosis |journal = The New England Journal of Medicine |volume = 358 |issue = 21 |pages = 2240–2248 |doi = 10.1056/NEJMoa0802315 |pmid = 18441370 |pmc = 2829748 |display-authors = etal }}</ref><ref name="Maguire 2009">{{cite journal |author1 = Maguire A. M. |author2 = High K. A. |author3 = Auricchio A. |author4 = Wright J. F. |author5 = Pierce E. A. |author6 = Testa F. |author7 = Mingozzi F. |year = 2009 |title = Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial |journal = Lancet |volume = 374 |issue = 9701 |pages = 1597–1605 |doi = 10.1016/S0140-6736(09)61836-5 |pmid = 19854499 |display-authors = etal |pmc = 4492302 }}</ref> and functional mobility<ref name="Maguire 2008" /><ref name="Maguire 2009" /><ref name="Bainbridge 2008">{{cite journal |author1 = Bainbridge J. W. B. |author2 = Smith A. J. |author3 = Barker S. S. |author4 = Robbie S. |author5 = Henderson R. |author6 = Balaggan K. |author7 = Viswanathan A. |year = 2008 |title = Effect of gene therapy on visual function in Leber's congenital amaurosis |url = http://cvrl.ioo.ucl.ac.uk/people/stockman/pubs/2008%20gene%20therapy%20b%20et%20al.pdf |journal = The New England Journal of Medicine |volume = 358 |issue = 21 |pages = 2231–2239 |doi = 10.1056/NEJMoa0802268 |pmid = 18441371 |hdl = 10261/271174 |display-authors = etal |url-status = live |archive-url = https://web.archive.org/web/20170811191322/http://cvrl.ioo.ucl.ac.uk/people/Stockman/pubs/2008%20Gene%20therapy%20B%20et%20al.pdf |archive-date = 11 August 2017 |citeseerx = 10.1.1.574.4003 }}</ref> as well as objective measures that are less susceptible to bias, such as the pupil's ability to respond to light<ref name="Cideciyan 2009" /><ref name="Hauswirth 2008">{{cite journal |author1 = Hauswirth W. W. |author2 = Aleman T. S. |author3 = Kaushal S. |author4 = Cideciyan A. V. |author5 = Schwartz S. B. |author6 = Wang L. |author7 = Conlon T. J. |year = 2008 |title = Treatment of Leber Congenital Amaurosis Due to RPE65Mutations by Ocular Subretinal Injection of Adeno-Associated Virus Gene Vector: Short-Term Results of a Phase I Trial |journal = Human Gene Therapy |volume = 19 |issue = 10 |pages = 979–990 |doi = 10.1089/hum.2008.107 |pmid = 18774912 |pmc = 2940541 |display-authors = etal }}</ref> and improvements on functional MRI.<ref name="Ashtari 2011">{{cite journal |author1 = Ashtari M. |author2 = Cyckowski L. L. |author3 = Monroe J. F. |author4 = Marshall K. A. |author5 = Chung D. C. |author6 = Auricchio A. |author7 = Simonelli F. |year = 2011 |title = The human visual cortex responds to gene therapy-mediated recovery of retinal function |journal = The Journal of Clinical Investigation |volume = 121 |issue = 6 |pages = 2160–2168 |doi = 10.1172/JCI57377 |pmid = 21606598 |pmc = 3104779 |display-authors = etal }}</ref> Improvements were sustained over the long-term, with patients continuing to do well after more than 1.5 years.<ref name="Cideciyan 2009" /><ref name="Simonelli 2010" />

The unique architecture of the retina and its relatively immune-privileged environment help this process.<ref>{{cite journal |author = Bennett J |year = 2003 |title = Immune response following intraocular delivery of recombinant viral vectors |journal = Gene Therapy |volume = 10 |issue = 11 |pages = 977–982 |doi = 10.1038/sj.gt.3302030 |pmid = 12756418 |doi-access = free }}</ref> [[Biology:Tight junction|Tight junction]]s that form the blood retinal barrier separate the subretinal space from the blood supply, thus protecting it from microbes and most immune-mediated damage, and enhancing its potential to respond to vector-mediated therapies. The highly compartmentalized anatomy of the eye facilitates accurate delivery of therapeutic vector suspensions to specific tissues under direct visualization using microsurgical techniques.<ref>{{cite journal |author1 = Curace Enrico M. |author2 = Auricchio Alberto |title = Versatility of AAV vectors for retinal gene transfer |doi = 10.1016/j.visres.2007.07.027 |pmid = 17923143 |date = 2008 |journal = Vision Research |volume = 48 |issue = 3 |pages = 353–359 |s2cid = 9926758 |doi-access = free }}</ref> In the sheltered environment of the retina, AAV vectors are able to maintain high levels of [[Biology:Transgene|transgene]] expression in the retinal pigmented epithelium (RPE), photoreceptors, or ganglion cells for long periods of time after a single treatment. In addition, the eye and the visual system can be routinely and easily monitored for visual function and retinal structural changes after injections with noninvasive advanced technology, such as visual acuities, contrast sensitivity, [[Medicine:Fundus (eye)|fundus]] auto-fluorescence (FAF), dark-adapted visual thresholds, vascular diameters, pupillometry, [[Medicine:Electroretinography|electroretinography]] (ERG), multifocal ERG and [[Physics:Optical coherence tomography|optical coherence tomography]] (OCT).<ref name="Hollander2008">{{Cite journal |last1 = den Hollander |first1 = Anneke I. |last2 = Roepman |first2 = Ronald |last3 = Koenekoop |first3 = Robert K. |last4 = Cremers |first4 = Frans P.M. |year = 2008 |title = Leber congenital amaurosis: Genes, proteins and disease mechanisms |journal = Progress in Retinal and Eye Research |volume = 27 |issue = 4 |pages = 391–419 |doi = 10.1016/j.preteyeres.2008.05.003 |pmid = 18632300 |s2cid = 30202286 }}</ref>

This strategy is effective against a number of retinal diseases that have been studied, including neovascular diseases that are features of age-related macular degeneration, [[Medicine:Diabetic retinopathy|diabetic retinopathy]] and [[Medicine:Retinopathy of prematurity|retinopathy of prematurity]]. Since the regulation of vascularization in the mature retina involves a balance between endogenous positive growth factors, such as [[Biology:Vascular endothelial growth factor|vascular endothelial growth factor]] (VEGF) and inhibitors of [[Biology:Angiogenesis|angiogenesis]], such as pigment epithelium-derived factor (PEDF), rAAV-mediated expression of PEDF, angiostatin, and the soluble VEGF receptor sFlt-1, which are all antiangiogenic proteins, have been shown to reduce aberrant vessel formation in animal models.<ref name="Rolling2004">{{Cite journal |last = Rolling |first = F. |date = 2004 |title = Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives |journal = Gene Therapy |volume = 11 |issue = S1 |pages = S26–S32 |doi = 10.1038/sj.gt.3302366 |issn = 0969-7128 |pmid = 15454954 |doi-access = free }}</ref> Since specific gene therapies cannot readily be used to treat a significant fraction of patients with retinal dystrophy, there is a major interest in developing a more generally applicable survival factor therapy. [[Biology:Neurotrophic factors|Neurotrophic factors]] have the ability to modulate neuronal growth during development to maintain existing cells and to allow recovery of injured neuronal populations in the eye. AAV encoding neurotrophic factors such as fibroblast growth factor (FGF) family members and GDNF either protected photoreceptors from apoptosis or slowed down cell death.<ref name="Rolling2004" />

'''Organ transplantation'''
Transplantation of retinas has been attempted, but without much success. At [[Organization:Massachusetts Institute of Technology|MIT]], The University of Southern California, RWTH Aachen University, and the University of New South Wales, an "artificial retina" is under development: an implant which will bypass the photoreceptors of the retina and stimulate the attached nerve cells directly, with signals from a digital camera.

== History ==
Around 300 BCE, Herophilos identified the retina from dissections of cadaver eyes. He called it the ''arachnoid'' layer, from its resemblance to a spider web, and ''retiform'', from its resemblance to a casting net. The term arachnoid came to refer to a layer around the brain; the term ''retiform'' came to refer to the ''retina''.<ref>{{Cite journal|last=Dobson|first=J. F.|date=March 1925|title=Herophilus of Alexandria|journal=Proceedings of the Royal Society of Medicine|language=en|volume=18|issue=Sect_Hist_Med|pages=19–32|doi=10.1177/003591572501801704|pmid=19984605 |pmc=2201994 |issn=0035-9157}}</ref>

Between 1011 and 1021 CE, Ibn Al-Haytham published numerous experiments demonstrating that sight occurs from light reflecting from objects into the eye. This is consistent with intromission theory and against [[Physics:Emission theory (vision)|emission theory]], the theory that sight occurs from rays emitted by the eyes. However, Ibn Al-Haytham decided that the retina could not be responsible for the beginnings of vision because the image formed on it was inverted. Instead he decided it must begin at the surface of the lens.<ref>Sabra, A. I. (Ed.). (1011–1021/1989). The optics of Ibn Al-Haytham: Books I-III: On direct vision (A. I. Sabra, Trans.). The Warburg Institute.</ref>

In 1604, [[Biography:Johannes Kepler|Johannes Kepler]] worked out the optics of the eye and decided that the retina must be where sight begins. He left it up to other scientists to reconcile the inverted retinal image with our perception of the world as upright.<ref>{{Cite journal|url=https://jamanetwork.com/journals/jamaophthalmology/fullarticle/630807|access-date=2023-02-23|journal=Archives of Ophthalmology|doi=10.1001/archopht.1973.01000040061014|title=Kepler's Discovery of the Retinal Image |year=1973 |last1=Fishman |first1=R. S. |volume=89 |issue=1 |pages=59–61 |pmid=4567856 }}</ref>

In 1894, [[Biography:Santiago Ramón y Cajal|Santiago Ramón y Cajal]] published the first major characterization of retinal neurons in ''Retina der Wirbelthiere'' (''The Retina of Vertebrates'').<ref name="nobelprize.org">{{Cite web |title = Santiago Ramón y Cajal – Biographical |url = https://www.nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal-bio.html |website = www.nobelprize.org |access-date = 20 October 2015 |url-status = live |archive-url = https://web.archive.org/web/20151006122025/http://www.nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal-bio.html |archive-date = 6 October 2015 }}</ref>

[[Biography:George Wald|George Wald]], [[Biography:Haldan Keffer Hartline|Haldan Keffer Hartline]], and [[Biography:Ragnar Granit|Ragnar Granit]] won the 1967 Nobel Prize in Physiology or Medicine for their scientific research on the retina.<ref>{{cite web |url = http://nobelprize.org/nobel_prizes/medicine/laureates/1967/press.html |title = Nobelprize.org |website = nobelprize.org |access-date = 5 December 2017 |url-status = live |archive-url = https://web.archive.org/web/20170630125508/http://www.nobelprize.org/nobel_prizes/medicine/laureates/1967/press.html |archive-date = 30 June 2017 }}</ref>

A recent [[Organization:University of Pennsylvania|University of Pennsylvania]] study calculated that the approximate [[Bandwidth (computing)|bandwidth]] of human retinas is 8.75 megabits per second, whereas a [[Biology:Guinea pig|guinea pig]]'s retinal transfer rate is 875 kilobits per second.<ref>{{cite news |url = https://www.newscientist.com/article/dn9633-calculating-the-speed-of-sight.html |title = Calculating the speed of sight |newspaper = New Scientist |access-date = 5 December 2017 |url-status = live |archive-url = https://web.archive.org/web/20150531174437/http://www.newscientist.com/article/dn9633-calculating-the-speed-of-sight.html |archive-date = 31 May 2015 |last = Reilly |first = Michael }}</ref>

MacLaren & Pearson and colleagues at [[Organization:University College London|University College London]] and Moorfields Eye Hospital in London, in 2006, showed that photoreceptor cells could be transplanted successfully in the mouse retina if donor cells were at a critical developmental stage.<ref>{{cite journal |title = Retinal repair by transplantation of photoreceptor precursors |journal = Nature |doi = 10.1038/nature05161 |pmid = 17093405 |volume = 444 |issue = 7116 |date = November 2006 |pages = 203–207 |last1 = MacLaren |first1 = RE |last2 = Pearson |first2 = RA |last3 = MacNeil |first3 = A |display-authors = etal |bibcode = 2006Natur.444..203M |url = https://deepblue.lib.umich.edu/bitstream/2027.42/62596/1/nature05161.pdf |hdl = 2027.42/62596 |s2cid = 4415311 |hdl-access = free }}</ref> Recently Ader and colleagues in Dublin showed, using the electron microscope, that transplanted photoreceptors formed synaptic connections.<ref>{{Cite journal |last1 = Bartsch |first1 = U. |last2 = Oriyakhel |first2 = W. |last3 = Kenna |first3 = P. F. |last4 = Linke |first4 = S. |last5 = Richard |first5 = G. |last6 = Petrowitz |first6 = B. |last7 = Humphries |first7 = P. |last8 = Farrar |first8 = G. J. |last9 = Ader |first9 = M. |doi = 10.1016/j.exer.2008.01.018 |title = Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice |journal = Experimental Eye Research |volume = 86 |issue = 4 |pages = 691–700 |year = 2008 |pmid = 18329018 }}</ref>

In 2012, [[Biography:Sebastian Seung|Sebastian Seung]] and his laboratory at [[Organization:Massachusetts Institute of Technology|MIT]] launched EyeWire, an online [[Citizen science]] game where players trace neurons in the retina.<ref>{{cite web |url = http://eyewire.org/about/ |title = About: EyeWire |access-date = 26 March 2012 |url-status = dead |archive-url = https://web.archive.org/web/20120213150425/http://eyewire.org/about/ |archive-date = 13 February 2012 }}</ref> The goals of the EyeWire project are to identify specific cell types within the known broad classes of retinal cells, and to [[Biology:Brain mapping|map the connections]] between neurons in the retina, which will help to determine how vision works.<ref>{{cite web |url = http://eyewire.org/retina |title = Retina << EyeWire |access-date = 27 March 2012 |url-status = dead |archive-url = https://web.archive.org/web/20120324121236/http://eyewire.org/retina/ |archive-date = 24 March 2012 }}</ref><ref>{{cite web |url = http://eyewire.org/ |title = EyeWire |access-date = 27 March 2012 |url-status = live |archive-url = https://web.archive.org/web/20120424153908/http://eyewire.org/ |archive-date = 24 April 2012 }}</ref>

== Additional images ==
<gallery class="center">
File:Three Main Layers of the Eye.png|The structures of the eye labeled
File:Three Internal chambers of the Eye.svg|Another view of the eye and the structures of the eye labeled
File:Retinal Image.png|Illustration of image as 'seen' by the retina independent of optic nerve and striate cortex processing
</gallery>

== See also ==

{{Anatomy-terms}}
* Adeno associated virus and gene therapy of the human retina
* Charles Schepens – "the father of modern retinal surgery"
* [[Biology:Evolution of the eye|Evolution of the eye]]
* [[Biology:Duplex retina|Duplex retina]]
* [[Biology:Retinal scan|Retinal scan]]
* Retinal vein occlusion 
* List of xanthoma variants associated with hyperlipoproteinemia subtypes
* [[Biology:Rhodopsin|Rhodopsin]]
* [[Persistence of vision]]

== References ==
{{Reflist}}

== Further reading ==
* S. Ramón y Cajal, ''Histologie du Système Nerveux de l'Homme et des Vertébrés'', Maloine, Paris, 1911.
* {{cite journal |author = Rodieck RW |title = Quantitative analysis of cat retinal ganglion cell response to visual stimuli |journal = Vision Res. |volume = 5 |issue = 11 |pages = 583–601 |year = 1965 |pmid = 5862581 |doi = 10.1016/0042-6989(65)90033-7 }}
* {{cite book |author = Wandell, Brian A. |title = Foundations of vision |publisher = Sinauer Associates |location = Sunderland, Mass |year = 1995 |isbn = 978-0-87893-853-7 }}
* {{cite journal |vauthors = Wässle H, Boycott BB |title = Functional architecture of the mammalian retina |journal = Physiol. Rev. |volume = 71 |issue = 2 |pages = 447–480 |year = 1991 |pmid = 2006220 |doi=10.1152/physrev.1991.71.2.447}}
* {{cite journal |vauthors = Schulz HL, Goetz T, Kaschkoetoe J, Weber BH |title = The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium |journal = BMC Genomics |volume = 5 |issue = 1 |page = 50 |year = 2004 |pmid = 15283859 |doi = 10.1186/1471-2164-5-50 |pmc = 512282 |type = about a [[Biology:Transcriptome|transcriptome]] for eye colour |doi-access = free }}
* {{cite journal |last1 = Dowling |first1 = John |year = 2007 |title = Retina |journal = [[Scholarpedia]] |volume = 2 |issue = 12 |page = 3487 |doi = 10.4249/scholarpedia.3487 |bibcode = 2007SchpJ...2.3487D |doi-access = free }}

== External links ==
* [https://www.youtube.com/watch?v=nELWup_Gghw Histology of the Eye], edited by William Krause, Dept. Pathology and Anatomical science, University of Missouri School of Medicine
* [https://web.archive.org/web/20070314135325/http://neuro.med.harvard.edu/site/dh/index.html Eye, Brain, and Vision – online book – by David Hubel]
* Kolb, H., Fernandez, E., & Nelson, R. (2003). [http://webvision.med.utah.edu/ Webvision: The neural organization of the vertebrate retina]. Salt Lake City, Utah: John Moran Eye Center, [[Organization:University of Utah|University of Utah]]. Retrieved 22 July 2014.
* [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.figgrp.740 Retinal layers image.] NeuroScience 2nd Ed at United States National Library of Medicine
*[https://www.ibiology.org/neuroscience/color-vision/ Jeremy Nathans's Seminars: "The Vertebrate Retina: Structure, Function, and Evolution"]
* [http://ccdb.ucsd.edu/sand/main?mpid=54&event=displaySum Retina – Cell Centered Database]
* {{BUHistology|07901loa}}
* {{MedlinePlusEncyclopedia|002291}}

{{Eye anatomy}}
{{Visual pathways}}
{{Nervous system}}

[[Category:Visual system]]
[[Category:Human eye anatomy]]

{{Sourceattribution|Retina}}