Anatomy of Retina part 1
by Fejiri Mohammed
Ophthalmology resident (R1)
JUDO, July 2021
1
Outline
•Introduction
•Embryogenesis of retina
•Gross anatomy of retina
•Histology of Neurosensory retina
•Blood supply
•Clinical comments
•Summary
2
Introduction
•Retina is the inner most tunic of the eye ball.
•Thin delicate and semi transparent multi layered sheet of neural tissue .
•It appears purplish red due to visual purple of the rod
•Extends from OD to ora serrata, lines post. ¾ of eye wall
•It’s the most highly developed tissue of the eye.
3
Cont…
•Its thickness:
•at the posterior pole in the peripapillary region is approximately
0.56mm.
•At equator 0.18-0.2 mm
•At the ora serrata approximately 0.1mm
4
Embryology of Retina
Derived from:
•Neural ectoderm: optic cup
From two layers fold over one another
Cells join apex to apex, intraretinal space in between
Cells are ciliated in the inner surface, thin basal lamina at the outer
surface
•Neural crest cells: macroglia(Muller cell & astrocytes)
•Mesoderm: microglia, pericytes & vascular endothelial cells
5
6
•Optic pit-at 22day
•Optic vesicle-25 day
•Optic cup-4th wk
•NSR appose to RPE-30 day
•Optic fissure-close (5th-7th
wk) around the hyaloid
artery
NSR development
•Its inner layer of optic cup which is a single layered epithelium with internal and
external basement membrane .
•b/n week 4-6
8
•Primitiveretina(inner layer of optic cup) prolif. & differentiate into two zones:
Outer proliferative zone
Inner marginal zone
Cont…
•At week 7 inner and outer neuroblastic layers, with transient fiber layer of
Chievitz, a nucleus-free area b/n them will be formed by cell migration.
•Differentiation of the neural retinal cells begins in the central retina and
proceeds to the periphery.
•Ganglion cells and amacrine cells differentiate in the vitread portion of the
inner neuroblastic layer
•by week 8 the ganglion cells migrate and forms a layer close to the basement
membrane, and almost immediately send out their axonal processes,
9
Cont….
•By12 wksthe photoreceptors are aligned along the outer side of the inner
layer of the optic cup and adhering junctions will appear between them.
•These junctions form the precursor of the external limiting membrane.
10
11
Cont.….
By 5
th
month, all layers of adult retina are recognizable & apoptosis begins.
•Horizontal cell become distinguishable
•Microglia invade the retina
•Muller cell expansion below ILM & b/n rods & cones
By 6
th
monthNo further mitosis occur, Retinal growth continues by cell
differentiation, growth, and maturation.
12
13
Macular dev’t
•During the sixth month, cones begin to differentiate, and
•a dense accumulation of nuclei in the macular area makes this region
thicker than the rest of the retina;
•up to 8-9 rows of GC are evident
14
Cont…
Fovealdevelopment consists of three stages:
1, displacement of inner retinal components to form the depression;
2, migration of photoreceptors toward the center, which increases cone packing
3, maturation of the photoreceptor
•By 7 month GC and the cells of the INL begin to move to the periphery of the macula
•At birth-1GC layer & thin INL
•→ AT 4
th
m-only cone nuclei on foveal region
•The foveal depression continues to deepen until about age 15 months as cells continue to
move toward the macular periphery
15
Cont…
foveola: the retinal area of sharpest visual acuity, is the last to reach maturity.
•Comparedto that of the adult Before birth the rod free area is larger
•but it becomes narrower with migration of the cones centrally, increasing cone
density at center.
16
Retinal blood vessels development
17
At 5
th
week: Hyaloid vessels are within the optic stack
Early 4
th
month:
•Temporal clusters, or angiogenicbuds, develop from the hyaloid vessels at the OD.
•Which consists of endothelial cells, glial cells & macrophages
•The endothelial cells canalize & form new vessel
•Course along NFL toward peripheral retina at ~0.1mm/day, Reaches OS at 8
th
m
The intraneuralportion of the hyaloid artery will form the CRA
Vessels continue to develop until 3 month after birth.
Clinical comments
Retinopathy of prematurity
In premature infants exposed to a high O
2concentration
The immature vessels respond with vasoconstriction → cease to develop
On removal of O2 retinal tissue experience hypoxia →induce release of angiogenicfactor
→vasoproliferationof “leaky” vessels with poorly endothelial tight junctions.
Complications:
•Hemorrhage & retinal detachment(RD
•Neovascularinvasion of the vitreous
•Development of vitreoretinal adhesions
18
Congenital Anomalies
Retinal Dysplasia
•Aberrant differentiation in any cellular
layers.
•characterized by folds or rosettes(round
clumps) of retinal tissue
19
.
Myelinated Nerve Fibers
•Ganglion cells retaining myelin sheath
•bright white flame-shaped streaks
•usually contiguous with the margin of
the optic disc
20
Morning Glory Disc Anomaly
•is the result of abnormal development of the
distal optic stalk at its junction with the
primitive optic vesicle.
•The anomaly is typically unilateral and is
more common in girls.
•Serous retinal detachments occur in one-third
of cases
21
Cont….
•Bergmeister Papilla is a benign prepapillaryglial
remnant of the hyaloid artery, which is normally resorbed
before birth.
•Megalopapillais an abnormally large optic disc (area
>2.5 mm2).
•The commonly associated large cup can be mistaken for
glaucomatous damage
22
Gross Anatomy of retina
•Retina extend from optic disc to oraserataand has
surface area of about 266mm2 .
•Retina attachment sites
Optic disc
Ora serrata
Vitreous
•Grossly on ophthalmic fundus exam can be divided
into 3 regions.
•Optic disc
•Macula lutea
•Peripheral retina
23
Optic disc
•Pink, well defined circular area, 1.5mm diameter, slightly elongated vertically.
•Is the site where ganglion cell axons exit the eye
•All retinal layers terminate except the NFL and ILM
•In comparison to other retina, OD appear white due to
Lamina cribrosa
Medulatednerve fibers behind it
Absence of vascular Choroid & RPE
24
Cont.…
•Posses a central depression which is called Physiological cup,
•Central retinal vessels emerge through the center of this cup
•The cup varies in size, shape, position and depth in d/t eyes
•The nerve fibers are thinnest at the center -so white lamina shines more
brightly
•Grey spots in the lamina, if seen, are due to non-medullatednerve fibers
reflecting less light
25
Macula lutea
•Comparatively Dark area, 5.5 in
diameter at posterior pole, temporal to
OD
•Area centralis;
b/n the temporal retinal vascular
arcade, ellipsed
more than one layer of ganglion
cells
Responsible for photopic& color
vision
Corresponds to 15
0
of the visual
field
•Macular regions
26
Fovea centralis
•The central depressed part of the macula
•1.5mm in diameter & 0.25mm in thickness
•Corresponds to 5
0
of visual field & most
sensitive part of the retina
•Cones is the only photoreceptor
•Surrounding the fovea are
•parafoveal& perifovealareas of about
0.5mm & 1.5mm in diameter
12,7
27
Foveola
•0.35mm in d , forms centeral floor of the
fovea
•Its two disc diameter from edge of OD &
1mm below horizontal meridian
•0.1mm thick
•INL,IPL,GC are absent.
28
Umbo
•tiny depression at center of foveola
•correspond to visible foveolar reflex, in most of normal eyes
•loss may be early sign of damage
29
Cont…
Foveal avascular zone
•located inside fovea but outside foveola
•has variable diameter
•Its location can be determined with accuracy
only by fluorescein angiography
30
Peripheral retina
Divided into four regions
•Near periphery: 1.5mm ring peripheral to the temporal major vascular
arcades
•Mid periphery: occupies 3mm wide zone around the near periphery
•Far periphery : is aregionthat extend from optic disc ,9-10 mm on the
temporal side and 16mm on the nasal side in the horizontal meridian .
•Ora serrata: serrated peripheral margin where the retina ends and
cilirybody starts
31
Cont….
•2.1mm wide temporally & 0.7-0.8mm nasally
•From Schwalbe’s line: 5.75mm nasally and 6.5mm temporally
•Found 6-8mmaway from the equator approximately at the point of the
rectus muscle insertions
•At the ora,the sensory retina is firmly attached to both RPE and vitrious.
32
Retinal Histology
•Has 10 histologic ‘layerswith wo parts:
Retinal pigment epithelium (RPE
Neurosensory retina
•Neurosensory retina is composed of three elements:
Neuronal
Glial
Vascular
33
Retinal pigment epithelium
•It is the outermost layer of the retina
•Extends from the OD to the oraserrata, merge with PE of CB.
•Consists of a monolayer of hexagonal , pigmented cells
vary from 10 to 60 μm in diameter.
At fovea, taller & thinner, contain more & larger melanosomes
At periphery are shorter, broader, and less pigmented
•Adjecentcells are connected by tight junctions(ZO & ZA) soConstitutes the outer
blood-retinal barrier-
35
Photoreceptor layer
•Formed by the outer and inner segments of rods and cones.
•Projections from the apical surface of Müller cells that extend into the
photoreceptor layer and separate the inner segments .
•Rods and Cones are the end organs of vision
•Cones: responsible for photopic & color vision
•Rods:peripheral vision and vision of low illumination (scotopic vision
36
cont….
Parts of photoreceptor;
1.Inner & outer fiber
2.Cell body and nucleus
3.Inner & Outer segments
•form photoreceptor layer
37
External limiting membrane
•It is a fenestrated membrane through which processes of rods and cones pass
•Extends from ora serrata up to edge of OD
•Formed by junction (zonula adherents) b/n cell membrane of photoreceptors
& Muller’s cells
•It is not a true basement membrane
38
Outer nuclear layer
•Primarily formed by nuclei of rods & cones
•Rod nuclei form a bulk of ONL except at cones dominated foveal region,
•The number of rows of nuclei & thickness of this layer differs in d/t regions
•Nasal to the disc 8-9 layer of nuclei with 45µm thickness.
•Temporal to disc 4 rows of nuclei and 22 µm thickness
•Foveal region 10 row of nuclei with 50µm
•Rest of retina except ora serata 1 row of cone nuclei and 4 row of rod
nuclei with thickness of 27µm
39
Outer plexiform layer (OPL
•This layer contains : Synapses of rod spherules & cone
pedicles with the dendrites of bipolar and process of
horizontal cells
•Marks the junction of photoreceptors & first order
neurons in the retina
•Thickest at macula 51 µm and consists of Predominantly
oblique fibresthat have deviated from fovea also known
as Henle’s fiber layer
40
Inner nuclear layer (INL)
•Under microscope Resembles ONL except
it is very thin
•It disappear at fovea
•In other areas, it consists:
•Bipolar cell
•Horizontal cell
•Amacrine cell
•Soma of Muller’s cells
•Capillary of central retinal vessel
41
Cont…
Bipolar cells
•First order neurons of vision
•Their body consists entirely of nucleus, lei in INL
•Dendrites arborize with photoreceptor & horizontal cells in OPL
•Axons arborize with dendrites of ganglion cells & Amacrine cells in IPL
•Relay information from PR to horizontal, amacrine,andganglion cells and
receive extensive synaptic feedback from amacrine cells.
Has d/t classification –depending on morphology and synaptic relationships
42
Cont…
•Horizontal cell:
•transfers information in a horizontal direction parallel to the retinal surface
terminate in OPL.
•It has one long process, or axon, and several short dendrites with
branching terminals; synapse with
photoreceptors,
bipolar cells, and other horizontal cells.
•are joined to each other by an extensive network of gap junctions.
•most of the time one type of HC synapses only within a cone pedicle in
the special triad junction.
•d/t type of HC….
43
Cont….
Amacrine cell :
•Has a large cell body, and a single process with extensive branches that extend into the IPL.
•Their process has both dendritic and axonal characteristics and forms complex synapses
with
axons of bipolar cells,
dendrites and the soma of ganglion cells;
processes of interplexiformneurons; and
with other amacrine processes.
•Perform an integrative function, similar to horizontal cells
•Help to process signals by responding to specific alterations in retinal stimuli
sudden changes in light intensity or the presence of certain sizes of stimuli
44
Cont…
•Neuroglialcell:
•not actively involved in the transfer of neural signals,
•provide structural support and have a role in the neural tissue reaction to injury or
infection.
•Types of neuroglial cells found in the retina include Müller cells, microglial cells, and
astrocytes
Müller cells : are large neuroglial cells that extend throughout much of the retina.
•The apex of the Müller cell is in the photoreceptor layer, where as the basal aspect is at
the inner retinal surface.
•There are 10 million Müller cells in the mammalian retina.
•Cellular processes form a reticulum among the retinal cell bodies and fill in most of the
space of the retina not occupied by neuronal elements
45
Cont….
Microglial cells are wandering phagocytic cells and might be found any
where in the retina.
•Their number increases in response to tissue inflammation and injury.
Astrocytesare star-shaped fibrous cells found in the inner retina, usually in the
NFL and ganglion cell layers.
•These perivascular cells form an irregular supportive network that encircles nerve
fibers and retinal capillaries.
•They may contribute to the internal limiting membrane as well as perform some of
the same functions as the Müller cells
46
Inner plexiform layer
•TheIPL ( inner synaptic layer) consists of synaptic connections between the axons of
bipolar cells and dendrites of ganglion cells.
•Synapses also occur between
1, amacrine processes and bipolar axons,
2. amacrine processes and ganglion cell bodies and dendrites,
3.amacrine cells, and
4. amacrine cells and interplexiformneurons
•Generally, the axon of the invaginatingmidget bipolar cell ends in the inner half of the
IPL, and the axon of the flat midget bipolar cell ends in the outer half of the IPL.
47
Ganglion cell layer
•Composed of cell body & nuclei of
Ganglion cells
•2
nd
order neurons of visual pathway
•Single layer of cells in most parts of
retina, except:
•Macular region (6-8 layers)
•Temporal side of the disc (2 layers)
•Absent in the foveola
•separated from each other by glial processes
of Müller cells.
48
Nerve fiber layer
•Formed by axons of Ganglion cells (centripetal nerve fibers)that runs parallel to
the retinal surface;
•Pass through ON, chiasma & optic tract -synapse with cells in lateral geniculate
body (third order neuron)
•Un myelinated until passing the lamina cribrosa
•The NFL is thickest at the margins of the optic disc, where all the fibers
accumulate
49
Cont…
This layer also contains:
•Retinal vessels
•Superficial capillary network
•Process of Muller cells
Neuroglial cells
•Astrocytes -have structural role
•Microglia
•Respond to tissue injury (as histiocytes) and Phagocytes debris and carry to
the vasculature
50
Cont….
Arrangement of nerve fibers in retina
•Nerve fiber layer course parallel to retinal
surface
•From nasal half –direct as Superior & Inferior
radiating fibers
•From macular region –pass straight as
papillomacular bundle
•From temporal retina
Superior arcuate fibers
Inferior arcuate fibers
51
Cont….
Arrangement on entry to optic disc
Fibers from peripheral part lie
•deep in the retina &
•peripheral in the OD
Fibers closer to the ON head
•superficial in the retina &
•central in the OD
52
Cont…
Thicknessof NFL along the quadrants of the OD margin in (Decreasing
order)
•Upper & lower nasal quadrant
•Most medial quadrant
•Upper & lower temporal quadrants
•Most lateral quadrant
53
Cont…
Clinical significance
•Arcuate fibers are most sensitive to glaucomatous damage
•Early loss in corresponding Visual field
•Macular fibers are relatively resistant to glaucomatous damage
•Retaining central vision
•Papilledemaappear first in the thickest quadrant
54
Clinical Comments
•Retinal Hemorrhages have a characteristic
appearance because of nerve fibersarrangement
•Flame shaped: feathered pattern –in NFL
•Dot or blot: rounded –in the INL
55
Internal limiting membrane
•Forms the innermost boundary of the retina.
Consists of:
•Collagen fibrils ( type I & IV)
•Proteoglycans (hyalu. acid)
•The basement membrane
•Plasma membrane of Muller & other glial cells
•Anteriorly, is continuous with the internal limiting membrane of the ciliary body.
•It is present over the macula but undergoes modification at the optic disc, where
processes from astrocytes replace those of the Müller cells.
56
Clinical comments
Retinal Detachment (RD)
Occurs between RPE and NSR
Predisposing factors:
•No intercellular junctions b/n the two
•Firm attachment of RPE to Bruch’s
membrane and loose attachment of NSR
to RPE
Causes of RD can be:
•Rhegmatogenous
•Tractional
•Exudative
57
Cont….
Retinoschisis
•Is the separation of the layers of the NSR from one another
•The common site is the OPL
Metamorphopsia
•Disruption in the axis of the photoreceptor outer segment causes altered
vision
•Macular edemacan change the orientation of the photoreceptors
58
Retinal blood supply
Sources
•Central retinal artery (CRA)
•Choriocapillaries
•Cilioretinalartery (18-32%)
Outer 4 layers (RPE to ONL) get supply from Choriocapillaries
Inner 6 layers (OPL to ILM) are supplied byCentral retinal artery
OPL supplied partially from both-(choriocappilaryand CRA)
;watershade` zone
59
Cont….
Macular region gets supply by
•Branches of CRA
•Cilioretinalartery (sometimes)→Retain central vision in CRAO
Fovea is an avascular –from choriocapillaries
Retinal blood vessels end in loops before reaching the oraserrata
•OS is in a watershed zone; peripheral retinal degeneration is relatively
common
Retinal vessels are end arteries
60
Central retinal artery (CRA
•Arises from ophthalmic artery near optic
foramen
•Courses ahead with 5-6 right angle
bending sites until it reaches the OD
61
Cont…
•Out side optic nerve : 10-15mm behind eye ball along the inferomedial aspect of the
nerve it bend up ward to pierce the dura and arachinoid,
•receive covering from both dura and arachinoid
•In sub arachinoidspace : it bend forward and after short course again bend up ward at
nearly right angle and invaginatesthe pia to reach the center of nerve .
•clothed by the pia along with the pialvessels.
•it is also surrounded by sympathetic nerve plexus (nerve tiedman)
62
Cont….
•In the center of optic nerve : bend forward and accompany with vein which is on its
temporal side ,
•it passes anteriorly and pierces lamina cribrosato appear inside the eye .
•In the optic nerve head : it lies super ficiallyin the nasal part of physiologic cup,
covered by layer of glial tissue (connective tissue meniscus of khunt) which closes
the physiologic cup.
•Here it divides into two branches superior and inferior each of wichsub divided into
temporal and nasal near margin of optic disc.
63
Cont….
•In the retina : four terminal branches of CRA namely
SN,ST,IN,IT
•devided dichotomously as they proceed to
ward ora serata where they end with out
anastomosis .
64
Clinical comment
CRA Occlusion
•Is occlusion of CRA by emboli
•The macula may still be perfused
•Possible for good vision to be
maintained
65
Cont….
Retinal Veins (CRV)
•Is the only outflow channel for the retinal
circulation
•Drain to SOV/CS
CRVO
•Most frequent site of occlusion is at lamina
cribrosa
•Relative narrowing of CRA and vein contribute to
turbulent flow and an increased risk of thrombosis
especially if sclerotic and rigid.
66
cont…
Arteriovenous nicking
•Occurs when the arterial wall thicken and
constrict the vein at a crossing sites.
•Commonycaused HTN R
67
Retinal capillaries
•Terminal arteriole bend & dip vertically
into retina
•Form 2 capillary networks (in most
extra macular areas)
•Superficial capillary network lies in
NFL
•Deep capillary lies b/n INL & OPL
•More dense & complex
•At periphery, reduced to scanty single
layer
68
Cont…
•In the parafovealzone, well developed & 3
layered
•However, there is capillary free zone
(FAZ, d=500μm)
•In the peripapillary region, become 4 layered
•To support extremely thick NFL
69
Blood-Retinal Barrier
•Outer by RPE & inner by retinal vessels
•Prevents components of blood plasma from entering retinal tissue.
•Consists of:
•Zonula occludensjoining RPE cells
•Fenestrated choriocapillaries –allow large molecules to exit into
choroidal tissue
•Zonula occludensb/n endothelial cells of retinal capillaries.
70
summary
•Retina is a thin, delicate, transparent tissue that lines the inner posterior ¾ of eye
wall
•developed from inner & outer layers of optic cup
•Composed of RPE and NSR
•10 histological layers of retina
•NSR is composed of: Neuronal, Glial& Vascularelements
•Sources of Blood supply the retina
•Central retinal artery
•Choriocapillaries
•Cilioretinalartery
71
References
Anatomy and physiology of eye, A.K.Khurana
Clinical anatomy and physiology of visual system 3
nd
edition
BCSC 2019-2020
Duane's ophthalmology, 2012
72