3. Gross anatomy
• Extent: From optic disc to
ora serrata.
• Surface area: about 266
mm²
• Thickness: At the posterior
pole in peripapillary region
is approx. 0.56mm; at the
equator 0.18 to 0.2 mm;
and at ora serrata approx.
0.1 mm.
• Colour: Purplish-Red due to
visual purple of rods.
5. OPTIC DISC
• Pale-pink, Well defined circular
area of About 1.5mm diameter
• All the retinal layers terminate
except the nerve fibres which
pass through lamina cribrosa to
run into optic nerve.
• Physiological cup of the optic
disc is a depression seen in it.
The central retinal vessels
emerge from the centre of this
cup.
6. MACULA LUTEA
• 5.5 mm in diameter, lies
temporal to optic disc.
• Also called area centralis
• Corresponds to approx. 15 ͦ of
visual field.
• Primary functions are photopic
vision and colour vision.
• Oxygenated carotenoids, in
particular lutein and
zeaxanthine, accumulate
within the central macula and
cause yellow colour.
• 3 main areas: Fovea,
Parafovea, Perifovea.
7. FOVEA CENTRALIS
• Central depressed part of
macula
• 1.5mm in diameter,
1.55mm in thickness
• Corresponds to 5 ͦ of
visual field.
• Most sensitive part of
Retina.
8. FOVEOLA
• 0.35 mm in diameter, 0.15mm
thick
• Central floor of the fovea
• 2 Disc Diameter(3mm) away
from temporal edge of optic disc.
• Inner nuclear layer and ganglion
cell layer is absent at foveola.
• Umbo is tiny depression in the
centre of foveola. Greatest
concentration of cones is found
in umbo, thus, referred to as
Central bouquet of cones.
• FAZ: Foveal Avascular zone:
central avascular region is known
as the foveal avascular zone
(FAZ).
• The absence of blood vessels
and overlaying inner retinal
tissue are thought to maximize
the optical quality of the foveal
pit by reducing light scattering.
9. PARAFOVEA
• 0.5 mm wide belt that
surrounds the foveal
margin.
• Ganglion cell layer,
inner nuclear layer and
henle’s layer are
thickest (i.e. the retina
is the thickest)
PERIFOVEA
• 1.5mm wide belt
surrounding parafoveal
region
10. PERIPHERAL RETINA
• Near Periphery: 1.5mm wide area around macula
• Mid Periphery: 3mm wide zone around the near periphery. Its
outer limit corresponds to the equator.
• Far Periphery: Extends from equator to ora serrata. Width is 6mm.
The peripheral retinal pathologies are measured in clock hours. 1
clock hour corresponds to 5-6mm. So the peripheral retinal belt can
be divided into 12 squares of 6X6mm.
• Extreme periphery: Area of pars plana and ora serrata.
12. Retinal pigment epithelium (RPE)
• Outermost layer of retina
• Made up of single layer of hexagonal
cells containing pigments
• Firmly adherent to the underlying
Bruch's membrane & loosely
attached to layer of rods and cones
• Sub-retinal space: Potential space
between RPE & sensory retina.
Contains Sub-retinal fluid.
• Retinal detachment: Separation of
RPE from sensory retina
• Melanin granules are concentrated
in apical end of each RPE cell.
• Lipofuscin is another major RPE
pigment which accumulates with
age.
RPE aligned alongside CC, Choriocapillaris;
BM, Bruch’s membrane; RPE. retinal
pigment epithelium; ap, apical processes;
os, outer segments; C, cones. R, rods.
13. Functions of RPE
• Renewal of photoreceptor & recycling of Vit. A i.e. visual
pigment
• Provides mechanical support to processes of photoreceptors
• Manufacturing of pigments which absorb light
• Phagocytosis and digestion of photoreceptors
• Maintains Subretinal space by forming outer Blood-retinal
barrier and pumping ions and water out of this space.
• Transport of nutrients across blood retinal barrier.
• Regenerative and reparative function after surgery and injury.
14. Layer of Rods & Cones
• Rods & cones transform
light energy into visual
(nerve) impulses
• Rods contain
photosensitive substance
rhodopsin whereas cones
contain photosensitive
substance iodopsin
• Cone cells – Central vision
and photoptic vision
• Rod cells – Peripheral vision
and scotopic vision
15. Structure of Rod cell
• Length :- 40-60 um
• Outer segment is cylindrical composed of numerous
lipid protein lamellar discs
• 600- 1000 discs/rod
• Discs contain 90% of visual purple
• Inner segment :- consist of ellipsoid & myoid region.
Ellipsoid is rich in mitochondria and myoid is rich in
golgi bodies and other cell organelles.
• Outer rod fibre arises from inner segment of rod,
passes through external limiting membrane and
further swells into densely stained nucleus .
• The nucleus terminates further into inner rod fibre
• The inner rod fibre ends as a bulb called rod spherule.
16. Structure of Cone cells
• Length :- 40-80um
• At periphery :- 40um ( shortest)
• At fovea :- 80um (longest)
• Outer segment is conical, shorter than rod
and contains iodopsin pigment packed in
lamellar discs
• 1000-1200 discs/cone
• Inner segment is similar to rods
• Inner segment is directly continuous with
nucleus
• A stout cone inner fibre runs from the
nucleus & has lateral processes at the end
called cone foot or cone pedicle
17. Rods and cone density in retina
Distribution of cones
• Highest at fovea
• 1-3lakh/mm² at fovea
• Rapidly decrease from
fovea
• 6000/mm² at 3mm away
from fovea
Distribution of rods
• Lowest at fovea
• 0.35mm rod free zone
• Maximum below the Optic
Nerve- 1,70,000/mm²
• Number reduced towards
periphery
18. External limiting membrane
• Fenestrated
membrane extending
from the ora serrata
upto the edge of
optic disc
• Processes of rods &
cones pass through it
• Junction between
the cell membrane
of photoreceptors &
Muller’s cell
19. Outer nuclear layer
• Made up of the nuclei of
rods & cones
• Rod nuclei form the bulk of
this layer except at cone
dominated foveal region
Outer plexiform layer
• This layer is made of
synapses between the rod
spherules & cone pedicles
with the dendrites of bipolar
cells and processes of
horizontal cells.
• Thickest at macula, also
called as henle’s layer.
20. Inner nuclear layer
• It is very thin.
• Disappears at fovea.
• It consists of:
Bipolar cells
Horizontal cells
Amacrine cells
Muller’s cells
Capillaries of the Central retinal vessels
21. BIPOLAR CELLS
• Neurons of first order of vision.
• Body of the bipolar cells consists entirely of nucleus. Their dendrites
arborize with the rod spherules and cone pedicles in outer
plexiform layer.
• Under light microscopy nine types
a. Rod bipolar cells– arborise only with rod spherules
b. Invaginating midget bipolar
c. Flat midget bipolar
d. Invaginating diffuse bipolar
e. Flat diffuse bipolar
f. On-centre blue cone bipolar
g. Off-centre blue cone bipolar
h. Giant bistratified bipolar
i. Giant diffuse invaginating bipolar
Make connections only with the triads of
cone pedicle
Make connections with cone pedicle
only but not with their triad.
Innervate more than 1 cone pedicle
22. AMACRINE CELLS
• Flat cells having numerous horizontal
associative and neuronal
interconnections between photo
receptors and bipolar cells in the outer
plexiform layer.
• Type A: Have contact with cone cells only
• Type B: Have contact with rod cells only
HORIZONTAL NEURONS
• They have a piriform body and single
process.
• Form connections with the axons of
Bipolar cells and the dendrites of
ganglion cells in the Inner Plexiform
Layer.
23. MULLER’S CELLS
• They provide structural support and
contribute to metabolism of sensory retina.
• Take part in formation of external and
internal limiting membrane.
• Form horizontal extending reticulum in outer
and inner plexiform layer.
• Muller cells express voltage-gated ion
channels, neurotransmitter receptors and
various uptake carrier systems. These
properties enable the Muller cells to control
the activity of retinal neurons by regulating
the extracellular concentration of neuroactive
substances such as K+, GABA and glutamate.
• Muller cells provide trophic and anti-oxidative
support of photoreceptors and neurons and
regulate the tightness of the blood-retinal
barrier.
24. Inner Plexiform Layer
• Synapses between Axons
of Bipolar cells (1st order
neurons), dendrites of
Ganglion cells (2nd order
neurons) and the
processes of Amacrine
cells.
• Also contains processes
of Muller cells which form
horizontal extending
reticulum.
• This layer is absent at
Foveola.
25. GANGLION CELL LAYER
• Cell bodies and nuclei of ganglion cells lie in this layer.
• Composed of single row of cells except in macula where it is
multi layer and on temporal side of disc it has two layers.
• It is absent at foveola .
• Classification of ganglion cells:
a. w, x, y ganglion cells
b. P & M ganglion cells
c. Off centre & on centre
d. Mono & Polysynaptic
26. NERVE FIBRE LAYER
• Consists of unmyelinated axons of the
ganglion cells which converge at the optic
nerve head, pass through the lamina
cribrosa and become ensheathed by myelin
posterior to the lamina cribrosa.
• Also contains Muller cells which interweave
with the axons of ganglion cells.
• Neuroglial cells are also present. They can
be macroglia, which have a structural role,
or microglia, which play a role during tissue
injury and phagocytose the debris.
• Retinal vessels lie in this layer. A rich bed of
superficial capillary network is present in
this layer.
27. ARRANGEMENT OF NERVE FIBRES IN
THE RETINA
• From nasal half of the retina
come directly to the optic disc
as superior and inferior
radiating fibres (srf and irf)
• From macular region pass
straight in the temporal part of
the disc as papillomacular
bundle (pmb)
• From temporal retina arch
above and below the macular
and papillomacular bundle as
superior and inferior arcuate
fibres (saf and iaf) with a
horizontal raphe in between.
28. ARRANGEMENT OF NERVE FIBRES OF THE
OPTIC NERVE HEAD
Most lateral quadrant (thinnest)
Upper temporal and lower temporal
quadrant Most medial quadrant
Upper nasal and lower nasal
quadrant (thickest)
THICKNESS OF NERVE
FIBRE LAYER AT THE DISC
• Fibres from the peripheral part of the retina lie deep in the retina
but occupy the most peripheral (superficial) part of the optic disc.
• Fibres originating closer to the optic nerve head lie superficially in
the retina and occupy a more central (deep) portion of the disc.
29. CLINICAL SIGNIFICANCE OF DISTRIBUTION AND
THICKNESS OF NERVE FIBRES AT THE OPTIC
DISC MARGIN
• Papilloedema appears first of all in the thickest quadrant
(upper nasal and lower nasal) and last of all in the thinnest
quadrant (most lateral).
• Arcuate nerve fibres which occupy the superior temporal and
inferior temporal quadrants of optic nerve head are most
sensitive to glaucomatous damage, accounting for an early
loss in corresponding regions of visual field.
• Macular fibres occupying the lateral quadrant are most
resistant to glaucomatous damage and explain the retention
of the central vision till end.
30. INTERNAL LIMITING MEMBRANE
• Consists of PAS positive true basement membrane that forms
the interface between retina and vitreous.
• It consists of Collagen fibrils, Proteoglycans, Basement
Membrane, Plasma Membrane of the Muller cells and
possibly other glial cells of the retina.
32. Blood–Retinal Barrier
• The BRB consists of inner and outer components (inner BRB [iBRB]
and outer BRB [oBRB])
• It regulates fluids and molecular movement between the ocular
vascular beds and retinal tissues and prevents leakage into the
retina of macromolecules and other potentially harmful agents.
Inner BRB
• Tight junctions (zonulae
occludentes) between
neighboring retinal capillary
endothelial cells.
• Continuous endothelial cell
layer, which forms the main
structure of the iBRB, rests on a
basal lamina that is covered by
the processes of astrocytes &
Müller cells & Pericytes
Outer BRB
• Tight junctions (zonulae
occludentes) between neighbouring
retinal pigment epithelial (RPE) cells.
• Separates the neural retina from the
fenestrated choriocapillaris
• Regulating access of nutrients from
the blood to the photoreceptors, as
well as eliminating waste products
and maintaining retinal adhesion.
36. Vitamin A
Dietary Vit. A (Carotenes in plant food
and retinol in animal food)
Maintenance of healthy Corneal and
conjunctival epithelium
Formation of rhodopsin used
in night vision in outer segment
of photoreceptors
Transport of retinol bound to Retinol Binding Protein
Production of Retinol Binding
protein – The Carrier ProteinRetinol- Storage form of Vit. A in liver cells
Digestion and absorption of Vit. A from food in intestine
37. Visual Pigments
• Also known as visual purple
• Present in the outer segment of rods
• photopsin + retinol = Rhodopsin
• Rhodopsin protein is insoluble in water, But
sensitive to strong acids & alkalis
• Peak sensitivity : 493- 505nm
• Absorbs yellow wavelength of light
• transmits violet to red colour - hence appears
visual purple
Rhodopsin
38. Cone pigments
• 3 kinds of cones.
• Responsible for colour vision
• Respond to different
wavelengths of light, giving
rise to colour vision.
• Peak absorbance:-
– Blue sensitive cones:- 435
nm
– Green sensitive cones:-
535 nm
– Red sensitive cones:-580
nm
39. Light Induced changes
(In Rod cells)
• Rhodopsin bleaching
• Rhodopsin regeneration
• Visual cycle
• Phototransduction
• Photochemistry of photoptic vision
40. Rhodopsin Bleaching and Regeneration
Rhodopsin
Lumirhodopsin
Metarhodopsin I
Metarhodopsin II
(ACTIVATED RHODOPSIN)Opsin
Isomerase
11 cis-retinal
11 cis-retinol All trans-retinol
All trans-retinal
NAD
NADH
Barthorhodopsin
NAD
NADH
Isomerase
Rhodopsin
Regeneration Photodecomposition
41. Visual cycle- Scotopic vision
•Equilibrium between photodecomposition and regeneration of
visual pigments is referred to as visual cycle
ACU-4429, a small nonretinoid molecule, is a modulator of the isomerase (RPE65) required for the
conversion of all-trans-retinol to 11-cis-retinal in the RPE. By modulating isomerization, ACU-4429 slows the
visual cycle in rod photoreceptors and decreases the accumulation of retinal toxic by-products like A2E.
42. Scotopic visual process
RODS:-
• contain the photo pigment rhodopsin, which breaks down when
exposed to a wide bandwidth of light (i.e., it is achromatic).
– Rhodopsin is also more sensitive to light and reacts at lower light
levels than the colour sensitive (chromatic) cone pigments.
• have longer outer segments, consequently, contain more photo-
pigment.
• are more sensitive to light and function at scotopic (low) levels of
illumination.
• dominate in the peripheral retina, which is colour insensitive, has
poor acuity , but is sensitive to low levels of illumination.
43. Photopic Visual process
• Like rhodopsin, cone pigments also consists of protein opsin, i.e photopsin
& retinine
• Photopsin differs slightly from rhodopsin in that it is colour sensitive i.e.
chromatic
• 3 classes of photopsin :-
– Erythrolabe – red sensitive
– Chlorolabe – green sensitive
– Cyanolabe – blue sensitive
Cones:-
• are less sensitive to light and require high (daylight) illumination levels.
• are concentrated in the fovea.
• in the fovea are responsible for photopic, light-adapted vision (i.e., high
visual acuity and colour vision) in the central visual field.
44. Visual Adaptation
• Human visual system is sensitive to a range of illumination to
be capable of functioning in various illuminations.
• Visual adaptation Types:
1. Light Adaptation
2. Dark Adaptation
45. Light Adaptation
• Light adaptation is the ability of the eye to adjust
in bright light.
• Promptly occurring over a period of 5 minutes.
• Dark Adaptation is the ability of the eye to
recover its sensitivity in the dark after being
exposed to bright light, making vision possible in
relative darkness
Dark Adaptation
46. Prolonged stay in dark
Regeneration of bleached pigments in the retina
11-cis retinal uptake from RPE cells- Rate limiting
Rhodopsin formation and cone-pigment formation
Increased sensitivity of rods and cones to light
Proportional to amount of pigment
•↑ Pupil size- ↑ incoming light by 30X
•Feedback inhibition of bipolar cells
Ability to see images in dark
Dark adaptation
47. Movement towards light
Bleaching of pigments in the retina
Rhodopsin bleaching happens quickly and rods get saturated
Cone-pigment bleaching over a period of time according to light intensity
Decreased sensitivity to light
Proportional to amount of light
•↓ Pupil size- ↓ incoming light
• Neural adjustment of light sensitivity
Adjustment to bright light to see images clearly
Light adaptation
48. Standing current or Dark current
• Normally, the inner segment of photoreceptor
continually pumps Na+ from inside to outside, thereby
creating a negative potential on the inside of the entire
cell.
• The Na+ channels present in the cell membrane of the
outer segment of photoreceptor are kept open by
Cyclic-GMP, in the dark.
• So, the cell membrane in outer segment is
Hypopolarised with respect to the inner segment i.e.
The current flows from the inner to the outer segment.
This is called Standing Potential or Dark Current.
49.
50. Phototransduction
• Translation of
information
content of light
stimulus into
electric signals
Rhodopsin
Metarhodopsin II
Activation of transducin
Activation of Phosphodiesterase
Decreased intracellular cGMP
Closure of Na+ channels
Hyperpolarization
(Local graded potential)
Decreased release of synaptic neurotransmitter
Response in bipolar cells
51. Neurotransmitters in Retina
• Glutamine: Excitatory, released by rods and cones at their
synapses with horizontal and bipolar cells.
• Amacrine cells release multiple neurotransmitters.
Gamma Amino Butyric Acid(GABA), Glycine, Dopamine,
Acetylcholine, Indolamine and Serotonine are inhibitory in
nature.
Nitric Oxide is excitatory in nature.
• Acetylcholinestrase has been found in the processes of
Muller, horizontal, amacrine and ganglion cells; suggesting
that Acetylcholine may be the dominant synaptic
neurotransmitter in the human.
• Carbonic Anhydrase has been isolated from cones and RPE
but not rods. Its exact role is not clear.
52. Signal processing in retina
Photoreceptors
Glutamate --> neurotransmitter released from
all photoreceptor cells
On-center Bipolar cellsOff-center Bipolar cells
• Depolarized by Glutamate
and in dark conditions
• Cone cells- 1- few cells
/cone-bipolar cells
• Hyperpolarized by Glutamate
and depolarized in light
conditions
• Cone cells- 1-few cells/cone-
bipolar cell
• Rod cells- 1-50 cells /rod-
bipolar cells
Spatial summation
Horizontal cells
- In outer plexiform layer
- Lateral inhibition of surrounding cells
- Contrast enhancement
- Spatial information processing
53. Amacrine cells
- Temporal processing
- Negative feedback arrangement
- Initial analysis of visual signals
Ganglion cells
- Generate signal impulse for brain
- 3 types
W-Ganglion cells
- <10um
- 40%
- Receive excitation from Rods
- Rod vision under dark
- Directional movements
X- Ganglion cells
- 10-15um
- 55%
- Input from cones
- Colour vision
- Visual image mainly
transmitted through these
cells
Y-Ganglion cells
- Upto 35um (Largest cells)
- 5% (fewest)
- Rapid changes in visual
image- movement or light
intensity
54.
55. Basic facts related to vision
• Visual acuity and colour vision are greatest in the
central visual field.
• The image of the central visual field is projected onto
the fovea.
• The cones are concentrated in the fovea, whereas the
rods predominate in the peripheral retina.
• There is low convergence of foveal cones onto macular
bipolar cells, as low as one cone receptor to one
bipolar cell.
56. Clinical Manifestations of Retinal Dysfunction
• Vitamin A deficiency
– produces degeneration of photoreceptors
with visual symptoms first presenting as
“night blindness” (i.e., extremely poor
vision under low illumination).
• Retinitis pigmentosa :
– Inherited disorder.
– Gradual and progressive failure to
maintain the receptor cells.
– One form involves the production of
defective opsin that normally combines
with 11-cis retinal to form rhodopsin.
– rods do not contain sufficient rhodopsin
and do not function as the low
illumination receptors.
– “night blindness” and loss of peripheral
vision.
57. • Age related Macular Degeneration. The
leading cause of blindness in the elderly is
age-related macular degeneration. The dry
form of macular degeneration involves
intraocular proliferation of cells in the
macular area (i.e., in the fovea and the
immediately surrounding retinal areas). In
the wet form of macular degeneration, the
capillaries of the choroid coat invade the
macular area and destroy receptor cells
and neurons. In both forms, the visual loss
is in the central visual field and the patient
will complain of blurred vision and
difficulty in reading.
• Retinal detachment. The neural retina is
detached from the retinal pigment
epithelium. The loss of vision results
because the neural retina is dependent on
the retinal pigment epithelium for 11-cis
retinal, nutrients and photoreceptor
integrity.
