The retina is essentially a piece of brain tissue that gets direct stimulation from the

outside worlds lights and images.

Theearliestsignofeyedevelopmentistheformationofthelensplacodes,
whicharesmallsurfaceectodermthickeningsonbothsidesofthedevelopinghead
(Table42).Atthesametime,theneuralectodermforms2opticpitsthatfillupto
formpouchesoneithersideofthe midline;these pouchesaretermedthe optic
vesicles.Thenarrowneckofthesevesiclesdirectlyconnectstheopticvesicleand
thedeveloping forebrain.Oncetheopticvesicletouchestheinneraspectof the
surfaceectoderm,thevesicleinvaginatestoformabilayeredopticcup;theinner
layerformstheneural retina, whereastheouter layer forms the retinalpigment

epithelium(RPE;Fig45).
Althoughthephysicalspacebetweenlayerseventuallycloses,itremainsa
potential space, given that retina detachments are commonly observed. As the
optic cup forms, 2 processes take place. First, the surface ectoderm begins to
invaginatetoformthelens.Second,the area be tweenthecup andthesurface
ectodermfillswithacombinationofmesodermalandneuralcrestderivedcells
theectomesenchymethatwillformmuchoftheanteriorsegmentoftheeye.
Theinvaginationoftheopticcupoccursasymmetrically(Figs46,47,4
8),withaventralfissurethatfacilitatesentryofmesodermalandneuralcrestcells
(Fig49).Thefissureclosesatitscenterfirstandthen"zips"bothanteriorlyand
posteriorly.Failureoffissureclosureleadstoacoloboma.Anteriorcolobomasare
the most common (they cause iris and occasionally anterior scleral defects);
central colobomas aretheleastcommon;and posterior colobomas occur witha
frequencysomewhereinbetween(theygiverisetoopticnerveheaddefects).The
locationoffissureclosurecorrelateswiththeinferonasalquadrant,whichiswhere
colobomasareclinicallyfound.
Retina and Posterior Segment
Theretinaformsas2overlappinglayers:(1)theneuralretinaformsfrom
the innersurface of the optic cup, whereas (2) the RPE forms from the outer
surface. The vitreous is likely formed by both mesodermal and ectodermal
components:neuralectodermcellsoftheinneropticcupprobablycontributethe
primary vitreous connective fibers, and the mesoderm forms the hyaloid
vasculature(Fig413).Theprimaryvitreousformsacentralconicalstructurethat
containsthehyaloidvasculatureandissurroundedbysecondary vitreous,which
eventuallyreplacestheprimary vitreous bythesixthfetalmonth. Thezonular

fibersofthelensalsodevelopatthistime;theyaredistinctfromtheprimaryand
secondaryvitreous.
Neural (inner) retinal development is drivenbyoverlappingcascadesof
geneticprograms;several"master"switcheshelpdeterminelineagesanddrive
cellfate,suchas Nrl(neuralretinalleucinezipper),atranscription factor of the
Maf subfamily that serves as an intrinsic regulator of rod photoreceptor
development.Retinaldevelopmentoccursconcentrically,beginninginthecenter
of the optic cup and extending peripherally. Lami nation of the neural retina
occursatapproximately812weeksofgestation.Ganglioncellsappeartobethe
firsttodifferentiate;theyproliferaterapidlyearlyinthesecondtrimester.The
internal andexternallimitingmembranesformwhencellsceasetoproliferate
andbegintodifferentiate.Retinalvasculaturefollowsthesameconcentricpattern
ofdevelopment.
TheRPEforms from proliferatingpseudostratifiedcolumnarepithelialcellsthat
createtightjunctionsanddepositabasementmembrane.TheBruchmembraneis
composedofSlayers:
1.

basementmembraneoftheRPE

2.

innercollagenouszone
3.elasticfibers4.outercollagenouszone
5.basementmembraneofthechoriocapillaris

TheRPEistheonlypigmentedtissueinthebodythatisnotderivedfromneural
crestcells,althoughthesecellsarelocatedattheanteriormostedgeoftheneural
crest,suggestingsharedevolutionaryorigins.

Theopticnervedevelopsfromtheopticstalk,whichisthenarrowstalkthat
connectstheopticvesiclewiththeforebrain.Theopticstalkishighlyactivein
regulating cell migration into and around the developing eye, mostly through
releaseofligandsandexpressionofgrowthfactorreceptors.Thestalkinitially
formsfromneuroectodermalcellssurroundedbyneuralcrestcells.Inthesixth
week of gestation, neuroectodermal cells begin to vacuolate and degenerate,
providing space for axons from the ganglion cells of the inner retina. The
surroundingneuralcrestcellsformmeninges,whereasneuroectodermalcellsform
surrounding oligodendrocytes (to make myelin sheaths) . Peripheral nerves,
includingmostcranialnerves,aresurroundedbymyelinsuppliedbySchwann
cells.Theexceptionistheopticnerve,whichissurroundedbyoligodendrocytes.
This difference is an important reason the optic nerve is susceptible to optic
neuritis.

Retina Pooyan669615267
The fundusoculi is thepartoftheeye that isvisiblewithophthalmoscopy;it
includes the retina, its vessels, and the optic nerve head, or optic disc. The
macula, 56mmindiameter,lies between thetemporalvasculararcades.Atthe
macula'scenter lies the fovea, whichisrichinconesandresponsibleforcolor
visionand the highest visual acuity. In the far periphery, the ora serrata (the
junctionbetweentheretinaandtheparsplana)canbeobservedwithgonioscopy
or indirect ophthalmoscopy. The reddish color of the fundus is due to the
transmissionoflightreflectedfromtheposteriorsclerathroughthecapillarybed
ofthechoroid.

The retina isa thin, transparentstructurethatdevelopsfrom the innerandouter

layersoftheopticcup.Incrosssection,fromoutertoinnerretina,the10layersof
theneurosensoryretinaare
3.

internallimitingmembrane

4.

nervefiberlayer

5.

ganglioncelllayer

6.

innerplexiformlayer

7.

innernuclearlayer

8.

middlelimitingmembrane

9.

outerplexiformlayer

10.

outernuclearlayer

11.

externallimitingmembrane

12.

rodandconeinnerandoutersegments
TheretinaisalsodiscussedindepthinBCSCSection12,RetinaandVitreous.
Retinal Pigment Epithelium
Thestructureoftheouterpigmentedepitheliallayerisrelativelysimplecompared
withthatoftheoverlying inner, or neurosensory,retina. TheRPEconsistsofa
monolayerofhexagonalcellsthatextendsanteriorlyfromtheopticdisctotheora
serrata,whereitmergeswith the pigmentedepitheliumof the ciliary body. Its
structureisdeceptivelysimpleconsideringitsmanyfunctions:
vitamin A metabolism maintenance of the outer bloodretina barrier
phagocytosisof the photoreceptoroutersegments absorptionoflight(reduction
ofscatter)
heat exchange formation of the basal lamina of the Bruch membrane
productionofthemucopolysaccharidematrixsurroundingtheoutersegments
activetransportofmaterialsintoandoutoftheRPE
Likeotherepithelialandendothelialcells,theRPEcellsarepolarized.Thebasal
aspectisintricatelyfoldedandprovidesalargesurfaceofattachmenttothethin

basallaminathatformstheinnerlayeroftheBruchmembrane(seeFig221).The
apiceshavemultiplevillousprocessesthatengagewiththephotoreceptorouter
segments. Separationofthe RPE fromtheneurosensoryretinaiscalled retinal
detachment.
ContiguousRPEcellsarefirmlyattachedbyaseriesoflateral,intercellularjunc
tional complexes. The zonulae occludentes and zonulae adherentes not only
providestructuralstabilitybutalsoplayanimportantroleinmaintainingtheouter
bloodretina barrier. Zonulae occludentes consist of fused plasma membranes
formingacircularbandorbeltbetweenadjacentcells.Asmallintercellularspace
ispresentbetweenzonulaeadherentes.
TheretinaandRPEshowimportantregionaldifferences(Fig227).Theretinais
thickestinthepapillomacularbundleneartheopticnerve(0.23mm)andthinnest
inthefoveola(0.10mm)andoraserrata(0.11mm).RPEcellsvaryfrom10to60
flmindiameter.ComparedwithRPEcellsintheperiphery,RPEcellsinthefovea
aretallerandthinner,containmoremelanosomes,andhavelargermelanosomes.
Thesecharacteristicsaccountinpartforthedecreasedtransmissionofchoroidal
fluorescence observed during fundus fluorescein angiography. Cells in the
periphery are shorter,broader,and less pigmented. The eyeofafetusorinfant
containsbetween4and6million RPEcells.Althoughthesurfaceareaoftheeye
increases appreciably with age, the increase in the number of RPE cells is
relativelysmall. No mitoticfiguresareapparentwithinthe RPE ofthenormal
adulteye.
The cytoplasm of the RPE cells contains multiple round and ovoid pigment
granules(melanosomes).Theseorganellesdevelopinsituduringformationofthe
opticcupand

Theretinaiscomposedof2laminarstructures:anouterretinalpigment
epithelium(RPE)andaninnerneuralretina.

Theinitiatingprocessofthecurrentsistheionicresponsestartedintherodsand
conesthatinfluencesthe ioniccurrent both directly by changesinNa+and K+
fluxesandindirectlybysynapticallymodifyingsecondorderretinalneurons.
ThechangesintheelectricalpotentialsoftherodsandconesareshowninFigure
127,whichdepictstheresponsesofrodsandconestoapulseoflightandapulse
ofdarkness. Light hyperpolarizes conesandrods.Thecone response israpid; it
turns offwhilethe light is still onandovershoots the darkpotential. The rod
responseismoreprolongedandturnsoffveryslowly.Darkdepolarizesthecone
andhaslittleinfluenceontherod,whichissaturatedathighlightlevelsandtoo
slow to respond to the shadow. The ionic changes are due to shifts in the
photoreceptors'conductivityofNa+andK+ions;thisconductivityisfacilitatedbya
cGMPgatedcationchannel(seeFig123).Theconcentrationgradientsforthese
ionsarereversedacrossthemembraneofthephotoreceptorssothatchangesinthe
conductivityoftheseionsmovecurrentsintheoppositedirections.

Rod Phototransduction

Catchinglightandconvertingitsminuteamountofenergyintoaneuralresponse
dis tinguishes the retina from all other neural structures, which it otherwise
resembles. This combined process occurs withina specializedorganelleofthe
photoreceptor cell, the outer segment. Most of our knowledge of
phototransductioncomesfrominformationknownaboutrods,whicharesensitive
nocturnallightdetectors.Considerablymorebiochemicalmaterialcanbeobtained
from rods than from cones because rods are much more numer ous in most
retinas. In addition, rods contain far more membrane than do cones, which
contributestotherods'highersensitivity.
Cone Phototransduction
Qualitatively, the phototransduction of cones resembles that of rods. Light
activated cone opsins initiate an enzymatic cascade that hydrolyzes cyclic
guanosine monophosphate(cGMP) and closes conespecific cGMPgatedcation
channels on the outersegment membrane. Cone phototransduction is
comparatively insensitive but fast and capable of adapting significantly to the
ambientlevelsofillumination.Thegreatertheambientlightlevelis,thefasterand
moretemporallyaccurateistheresponseofacone.Speedandtemporalfidelity
areimportantforallaspectsofconevision.Thisisonereasonvisualacuity

Retinal Electrophysiology Pooyan669615267

Changesinthelightfluxontheretinaproduceelectricalchangesinallof
theretinal cells, includingtheRPE andMullercells,aswell asneurons.These
electricalchangesresultfromioniccurrentsthatflowwhenionspecificchannels
areopenedorclosed.Thesecurrentsreachthevitreousandthecornea,wherethey
can be detected noninvasively by an electroretinogram (ERG) . The initiating
processofthecurrentsistheionicresponsestartedintherodsandconesthat
influencesthe ioniccurrent both directly by changesinNa+and K+ fluxesand
indirectlybysynapticallymodifyingsecondorderretinalneurons.
ThechangesintheelectricalpotentialsoftherodsandconesareshowninFigure
127,whichdepictstheresponsesofrodsandconestoapulseoflightandapulse
ofdarkness. Light hyperpolarizes conesandrods.Thecone response israpid; it
turns offwhilethe light is still onandovershoots the darkpotential. The rod
responseismoreprolongedandturnsoffveryslowly.Darkdepolarizesthecone
andhaslittleinfluenceontherod,whichissaturatedathighlightlevelsandtoo
slow to respond to the shadow. The ionic changes are due to shifts in the
photoreceptors'conductivityofNa+andK+ions;thisconductivityisfacilitatedbya
cGMPgatedcationchannel(seeFig123).Theconcentrationgradientsforthese
ionsarereversedacrossthemembraneofthephotoreceptorssothatchangesinthe
conductivity of these ions move currents in the opposite directions. (See also
BCSCSection12,RetinaandVitreous.)

Diagram of the 5 basic ERG responses defined by the International Standard for
Electroretinography. These waveforms and calibrations are exemplary only, as there is a

moderate range of normal values . The large arrowheads indicate the stimulus flash,
and the dashed lines show how to measure a-wave and b-wave amplitude and time-topeak (implicit time, 1). The implicit time of a flicker response is normally less than the
distance between peaks for stim ulation at 30 Hz