Editing Retina (section)

== 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 [[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 [[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 cell]]s have been shown to act as [[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 [[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 [[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 | publisher = Australian Museum | access-date = 5 December 2017 | archive-url = https://web.archive.org/web/20170912224747/https://australianmuseum.net.au/how-spiders-see-the-world | archive-date = 12 September 2017 | url-status = live }}</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 [[homology (biology)|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|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 [[Retina bipolar cell|bipolar]] and [[Retina horizontal cell|horizontal cells]] (yellow layer), then to the [[Retina amacrine cell|amacrine cells]] and [[Retinal ganglion cell|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 [[Santiago Ramón y Cajal|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:

# [[Inner limiting membrane]] – basement membrane elaborated by [[Muller glia|Müller cells]]
# [[Nerve fiber layer]] – axons of the [[Retinal ganglion cell|ganglion cell]] bodies (a thin layer of Müller cell footplates exists between this layer and the inner limiting membrane)
# [[Ganglion cell layer]] – contains nuclei of ganglion cells, the axons of which become the optic nerve fibres, and some displaced [[Retina amacrine cell|amacrine cells]]<ref name="eb" />
# [[Inner plexiform layer]] – contains the synapse between the [[Retina bipolar cell|bipolar cell]] axons and the dendrites of the [[Retinal ganglion cell|ganglion]] and amacrine cells<ref name="eb" />
# [[Inner nuclear layer]] – contains the nuclei and surrounding cell bodies (perikarya) of the [[amacrine cells]], [[Retina bipolar cell|bipolar cells]], and [[Retina horizontal cell|horizontal cells]]<ref name="eb" />
# [[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 [[macula]]r region, this is known as the f''iber layer of [[Friedrich Gustav Jakob Henle|Henle]]''.
# [[Outer nuclear layer]] – cell bodies of rods and cones
# [[External limiting membrane]] – layer that separates the inner segment portions of the photoreceptors from their cell nuclei
# [[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> 
# [[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 [[Retina bipolar cell|bipolar cells]]; transmission to [[Retinal ganglion cell|ganglion cells]], which also contain photoreceptors, the [[photosensitive ganglion cell]]s; and transmission along the optic nerve. At each synaptic stage,  [[Retina horizontal cell|horizontal]] and [[Retina amacrine cell|amacrine cells]] also are laterally connected.

The [[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 [[diencephalon]] (the rear of the forebrain). It also projects to the [[superior colliculus]], the [[suprachiasmatic nucleus]], and the [[nucleus of the optic tract]]. It passes through the other layers, creating the [[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 [[bird]]s, the [[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. [[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 [[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 [[macula]], at whose centre is the [[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 [[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 [[ora serrata]]. The distance from one ora to the other (or macula), the most sensitive area along the [[Meridian (perimetry, visual field)|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 [[nerve]] cells and two of [[synapse]]s, including the unique [[ribbon synapse]]. The optic nerve carries the [[Retinal ganglion cell|ganglion-cell]] [[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 [[retinal pigment epithelium]] or the [[choroid]] (both of which are opaque).

The [[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 [[blue field entoptic phenomenon]] (or Scheerer's phenomenon).

Between the [[Retinal ganglion cell|ganglion-cell]] layer and the rods and cones are two layers of [[neuropil]]s, where synaptic contacts are made. The neuropil layers are the [[outer plexiform layer]] and the [[inner plexiform layer]]. In the outer neuropil layer, the rods and cones connect to the vertically running [[Retina bipolar cell|bipolar cells]], and the horizontally oriented [[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 [[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 [[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 [[retinal mosaic|mosaic]] of sorts, transmission from receptors, to bipolars, to [[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 [[Retina horizontal cell|horizontal]] and [[Retina amacrine cell|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 [[optical coherence tomography]] (OCT), at least 13 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. |author-link4=Richard F. Spaide |year=2014 |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}}</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]]
[[Optical coherence tomography|on OCT]]
!Specific
anatomical

boundaries?
!Additional
references
|-
|1
|[[vitreous body|Posterior cortical vitreous]]
|Posterior cortical vitreous
|Hyper-reflective
|Yes
|<ref name=":0" />
|-
|''2''
|''[[Preretinal space]]''
|''In eyes where the [[vitreous body|vitreous]] has fully or partially [[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|| [[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" />
|-
|[[Nerve fiber layer]] (NFL)
|[[Ganglion cell]] [[axons]] travelling towards the [[optic nerve]]
|-
|4|| [[Ganglion cell layer]] (GCL) || [[Ganglion cell]] bodies (and some displaced [[amacrine cells]])
|Hypo-reflective
|
|<ref name=":0" />
|-
|5|| [[Inner plexiform layer]] (IPL) || Synapses between [[Retina bipolar cell|bipolar]], [[amacrine]] and [[ganglion cells]]
|Hyper-reflective
|
|<ref name=":0" />
|-
|6|| [[Inner nuclear layer]] (INL) ||a) [[Retina horizontal cell|Horizontal]], [[Retina bipolar cell|bipolar]] and [[amacrine]] cell bodies

b) [[Müller cell]] nuclei
|Hypo-reflective
|
|<ref name=":0" />
|-
|7|| [[Outer plexiform layer]] (OPL) || [[Synapses]] between [[Photoreceptor cell|photoreceptor]], [[Retina bipolar cell|bipolar]] and [[horizontal cells]]
|Hyper-reflective
|
|<ref name=":0" />
|-
| rowspan="2" |8||(Inner half) [[Henle's fiber layer|Henle's nerve fiber layer]] (HL)
| [[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) [[Outer nuclear layer]] (ONL)
|The [[Photoreceptor cell|photoreceptor]] cell bodies
|-
|9|| [[External limiting membrane]] (ELM)
| Made of [[zonulae adherens]] between [[Müller cells]] and [[photoreceptor inner segments]]
|Hyper-reflective
|
|<ref name=":0" />
|-
|10|| [[Myoid zone|Myoid zone (MZ)]] || The innermost portion of the [[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-access=free}}</ref>
|-
| rowspan="2" |11|| [[Ellipsoid zone|Ellipsoid zone (EZ)]] || The outermost portion of the [[Photoreceptor cell|photoreceptor inner segment (IS)]] packed with [[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 | first1=Jerome | last1=Sherman | first2=Daniel | last2=Epshtein | date=September 15, 2012 | 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|Photoreceptor integrity line (PIL)]]
|The photoreceptor [[Photoreceptor cell|connecting cilia]] which bridge the inner and outer segments of the photoreceptor cells.
|-
|12|| [[Photoreceptor cell|Photoreceptor outer segments (OS)]] || The [[Photoreceptor cell|photoreceptor outer segments (OS)]] which contain disks filled with [[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|Interdigitation zone (IZ)]] || Apices of the [[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" | [[Retinal pigment epithelium|RPE]]/[[Bruch's]] complex
  | [[Retinal pigment epithelium|RPE]] phagosome zone
  | '''Very Hyper-reflective'''
  | rowspan="3" | No
  | rowspan="3" | <ref name="sciencedirect.com"/><ref name=":0" />
|-
  | [[Retinal pigment epithelium|RPE]] melanosome zone
  | Hypo-reflective
|-
  | [[Retinal pigment epithelium|RPE]] mitochondria zone + Junction between the RPE & [[Bruch's membrane]]
  | '''Very Hyper-reflective'''
|-
|15
|[[Choriocapillaris]]
| colspan="2" |Thin layer of moderate reflectivity in inner choroid
|No
|<ref name=":0" />
|-
|16
|[[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 [[Sonic hedgehog|SHH]] and [[SIX3]] proteins, with subsequent development of the optic vesicles regulated by the [[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 [[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 [[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 [[Basic helix-loop-helix|bHLH]] and [[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 [[VAX1|VAX2]], whereas the N-T axis is coordinated by expression of the forkhead transcription factors [[FOXD1]] and [[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|
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[[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" />  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" /> 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 [[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 ===
{{See also|Retinal scan|Biometrics}}

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 [[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=[[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, [[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 |bibcode = 2013EnvHP.121.1011L }}</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>