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Physiology Of Retina

DR. PREETI AGARWAL

(1st year Resident)
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Presentation layout
• Introduction
• Physiology of the RPE/ Neural Retina
• Visual Cycle
• Phototransduction
• Information processing within the retina
• Light /Dark adaptation
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RETINA

• Retina: In latin “rete” means

net like.
• It has two main components:
- sensory layer
- pigmented layer
• It is the innermost tunic of
eyeball
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Light passes through most of

the retinal layers

Reaches and stimulates the

photoreceptor outer segment
discs

The neural flow then proceeds

back through the retinal
elements in the opposite
direction of the incident light
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Physiology of the RPE

 Absorption of scattered light
 Blood retinal barrier function
 Visual pigment regeneration and synthesis
 Synthesis of growth factors
 Maintenance of retinal adhesion
 Phagocytosis
 Electrical homeostasis
 Repair and regeneration after injury
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Absorption of light
• As a pigment layer of cells , it absorbs scattered
light to improve the optical quality.
• Light is absorbed by the melanin granule of
RPE leading to increase in temperature of the
RPE choroid complex.
• The heat is transported away by the bloodstream
in the choriocapillaris.
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Retinal Pigments
• Melanin
• Contain within the cytoplasmic granules of
melanosomes
• In old age, these pigments fuse with lysosome and
break down
• Absorb stray lights and minimize scatter within the eye
• Serves as a free radical stabilizer, bind toxins and
retinotoxic drugs
Tesselated fundus
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Retinal Pigments
• Lipofuscin
• Accumulates gradually with age
• Derived from
- the outer segment lipids that have
been ingested and then digested by
the RPE
- membrane fragments that have
been damaged by the light or
oxidation
• Clinically seen as Drusens
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Transepithelial transport
 RPE constitute a monolayer of cells; cuboidal in cross
section and hexagonal when looked from above

 Joined by the tight junctions ( zonulae occludens)

 Block the free passage of water and ions

 Equivalent to blood retinal barrier which are formed by

the capillary endothelium of intrinsic retinal vasculature.
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Transport from the blood side

Transport from the retinal side to
to the photoreceptor side the blood side

• Glucose transporters GLUT 1 • The retina is the tissue with the

and GLUT 3 highest density of cells.
• Neuronal cells show a high
• omega 3 fatty acid
metabolic activity, results in the
• retinal production of large amount of
water and accumulation of lactic
acid
• Also additional amount of water
are moved towards the retina by
intraocular pressure from
vitreous.
• Since RPE is tight epithelium
water cannot pass through
paracellular route.
• The transport of water is driven
by an active transport of Cl- from
the retina to the blood side
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CSCR (Central Serous Chorioretinopathy)

Serous detachment is not that fluid gets in ( given that a break is present in
RPE barrier) ,but that the fluid accumulates and persists (since the
powerful RPE would be expected to pump it right back)
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Visual pigment regeneration

Cellular retinaldehyde binding

protein(CRALBP)
Lecithin: retinol acyltransferase (LRAT)
Cellular retinol-binding proteins (CRBP )
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Phagocytosis of photoreceptors outer

segments
Light Oxygen
(radiant (from the
Source) choroid)

Photoreceptors Free
Radicals Damage Membranes
Production Over time
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• Everyday around 100 discs at the distal end of photoreceptors are

phagocytosed by the RPE while new discs are being synthesized
• Cell renewal process follows a cicardian rhythm : rod shed more
vigorously in the morning whereas cones shed more in the
darkness
• Within the RPE the phagocytosed disc becomes encapsulated in
vesicles called phagosomes

Merge with lysosome for digestion

Fatty acids are retained for recycling into outer segment

Waste or damaged membrane material is egested across the basal

RPE membrane
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Age Related Maculopathy

• RPE ingests and degrades rod outer segment , as
a consequence , lipofuscein accumulates in
RPE cells with age
• Oxidative stress ( light , smoking, low level of
antioxidant vitamins ) will increase lipofusin
accumulation as well as thickening of
extracellular matrix.
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Secretion
• The RPE is capable of secreting a large variety of growth factors,
cytokines or immune modulators.

• Growth factors elaborated by RPE serve not only to modulate the

behavior of RPE but also its surrounding tissues such as
choriocapillaries

• Functions:
 vascular supply
 permeability
 growth
 repair
 other processes vital to retinal function
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Growth Factors
Platelet Derived Growth Factor Modulates cell growth and healing
(PDGF)

Pigment Epithelium Derived Factor Neuroprotectant and vascular inhibitor

(PEGF)

Vascular Endothelial Growth Factor Stimulate normal or neovascular growth

(VEGF)

Fibroblast Growth Factor (FGF) Neurotropic

Transforming Growth Factor Moderates inflammation

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Age- related Macular Degeneration (AMD)

• One of the cause of irreversible visual loss in
industrialized countries
• Degenerative changes in the RPE cells,
extracellular matrix and possibly
choriocapillaries leads to malnutrition of
photoreceptors and RPE cells
• Two different responses to this malnutrition lead
to form two form of advanced AMD

AMD
Atrophic Form
• Characterised by
Insufficient production of
survival factors by damaged
RPE
• Leading to apoptosis of
functional complexes formed
by choriocapillaries, RPE and
photoreceptors
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Neovascular Type
• RPE and possibly
photoreceptors produce
excess VEGF
• Stimulates outgrowth of new
capillaries , CNV
• Clinically antagonists of VEGF
are injected in exudative AMD,
often stabiling or even
improving vision
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Retinal Adhesion
• Interphotoreceptor matrix (IPM) contain glycosaminoglycans
(GAGs) which surround rod and cones
• IPM functions:
• - physical support to the photoreceptors
• - transfer of nutrients and visual pigments
• - formation of an adhesive bond between retina and RPE
• The IPM function is largely controlled by RPE through
synthesis of matrix materials and transport proteins and also
through transport of ions and water.
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OTHER MECHANISM
• Vitreous gel
• Intraocular fluid pressure
• RPE water transport
• Mechanical interdigitation
Schaffer’s sign
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Electrical Activity In RPE

• Asymmetrical transport property of apical and basal
membrane generates transepithelial voltage(standing
potential)
• Light incident upon the photoreceptors causes the
potassium concentration of subneural retinal space falls
• Response: apical membrane of RPE and muller cell
hyperpolarizes
• Light activation of photoreceptors causes the release of
unknown messenger that causes the basal RPE
depolarization.
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Repair And Regeneration

• Although of neural origin the RPE are the pluripotent tissues
• Capable of local repair and cell migration
Examples
1. Laser burns: RPE surrounding the burn begin to divide
and fill the defect to form a new BRB within 1-2 weeks.
2. Retinitis pigmentosa: RPE migrate into the injured
neural retina and comes to rest around vessels to
contribute the characteristic bone spicule appearance
3. Macular degenerative process : vigorous RPE
response can lead to duplicated layers of RPE cells and
RPE scarring
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The most important function of RPE is the

ability to heal defects

Valuable in?

• photocoagulation for macular edema and

proliferative diabetic retinopathy

Dependent upon
• The ability of RPE cells to seal laser scars, re-establish
a degree of normal transport and avoid unnecessary
leakage of proteins into the subretinal space.
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PHYSIOLOGY OF NEURAL RETINA

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PHYSIOLOGY OF THE NEURAL RETINA

 80 to 110 million rods

 4 to 6 million cones

 Approximately 35 million bipolar cells

 1.12 to 2.22 million ganglion cells

 Signals from numerous photoreceptors converge at

one ganglion cell
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75,000 rods

5000 rod bipolar cells

250 amacrine cells

Single ganglion cell

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 Relatively small number of cones drive the cone

bipolar cell
 Small number of cone bipolar cells drive a single
ganglion cell
 In some situations, 1:1 ratio between cones and
ganglion cells
 Reflecting the significant amount of detail that
the cone population can discriminate
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Pathology
• Retinitis Pigmentosa
• Progressive Cone Dystrophy
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RHODOPSIN
• Present in outer segment of Rods
• OPSIN + RETINAL= RHODOPSIN
• It is insoluble in water
• Sensitive to acid and alkalis
• Absorbs yellow wavelength of light, transmits
violet to red colour, hence appears visual purple.
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Cone pigments
• 3 kinds:
• CYANOLABE : blue sensitive 435nm
• CHLOROLABE : green sensitive 535 nm
• ERYTHROLABE : red sensitive 580 nm
• Responsible for colour vision
• Cone pigments are different from Rhodopsin in
opsin portion , 11-cis retinal is same as
Rhodopsin
 Colour Blindness
Normal colour vision uses all three types of light
cones correctly known as Trichromacy
People with “faulty” trichromatic vision will be
colour blind
The different anomalous conditions are :
• PROTANOMALY RED-GREEN COLOUR BLIND
• DEUTERANOMALY
• TRITANOMALY
 NORMAL

RED- GREEN
BLUE DEFECT
DEFECT
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Opsin
Long helix
348 amino acids
• Loop seven times
• Determines the
wavelength absorbed by a
photoreceptor
• 11-cis-retinal, derivative of
vitamin A
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Phototransduction
• It is Series of biochemical events :

Release of
Photons captured Hyperpolarization
Neurotransmitter

• Photon of light is changed to an electrical signal

• Occurs in the photoreceptors
• Visual pigments in the photoreceptor outer segment
absorb light
• Initiates the process of vision
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VISUAL CYCLE
&
PHOTOTRANSDUCTION
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BLEACHING

REGENERATION
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The membrane potential

• Rods have resting membrane potential of -40mV
• Na+/K+ATPase pumps Na+ out of the cell and
K+ inside .
• K+ channels are predominant in resting state
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Incident Light ACTIVATION

CASCADE
Retinene1 changed to
All-trans form

Change in Opsin
Configuration

Transducin (Gα)
is activated

α-Subunit separates
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Subunit activates
cGMP PDE

Converts cGMP to
5’-GMP

Reduced cytoplasmic
cGMP

Closure of leaky
Na+ Channels

Hyperpolarization≈ -70 “Switching off”

mV
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Decrease intracellular
Ca2+

Decrease Glutamate
release

Electrical signal down

the neural pathway

Depolarization Hyperpolarization
(On Center bipolar (Off center bipolar
cells) cells)
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Bipolar Cells
• 1st order neuron in visual pathway
• Once a threshold is reached, the ganglion cell
responds and a signal is sent to higher CNS
locations
• Rod bipolars do not synapse with ganglion cells
directly but with amacrine cells
• TYPES
1. On Bipolar cells
2. Off Bipolar cells
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When Glu binds to the ionotropic receptor on a

bipolar dendrite

• Cation channels are opened in the cell membrane,

causing the bipolar cell to depolarize and release Glu

• This is an OFF bipolar because it is depolarized

in the dark
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When Glu binds to the metabotropic receptors on a

bipolar cell dendrite
• Decrease of cGMP occurs

• Closing cation channels in the cell membrane and

causing the bipolar cell to hyperpolarize
• Results in a decrease of glutamine release

• This is an ON bipolar because it is hyperpolarized in

the dark/ depolarized in the light
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OFF Bipolar On Bipolar

• Depolarizes in • Depolarizes in
dark light
• Hyperpolarize • Hyperpolarize
in light in dark

ON or OFF designation does not imply that the bipolar

itself is responding to the light condition; only
photoreceptors do that
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Amacrine Cells
• Receive information at
the synapse of the bipolar
cell axons with the
ganglion cell dendrites
• Bipolar cells project onto
both ganglion and
amacrine cells
• Negative feedback
• Reciprocal inhibition
• Works laterally
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Ganglion Cell
• Electrical response of bipolar cells after modification by
the amacrine cells
• Transmit the information by means of action potential

• Two types depending upon their response upon

illumination of the centre of receptive
1. on center
2. off center

• Three groups; W, X And Y ganglions

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Receptive Fields
Arranged in a center-surround pattern

• When light activates cells in the center of field, a given response

occurs

• When light falls on the surround , an antagonistic response occurs

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The center-surround
response occurs in part due
to

• Lateral inhibition by
horizontal cells

• Amacrine cell activity on

bipolar axon terminal
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The center-surround configuration allows a

neuron
• To respond to a direct message

• To gather information from neighboring areas

• Provide details e.g. detection of edges

• Maximizes retinal contrast sensitivity

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Seen at the level of

 Bipolar cells
 Ganglion cells
 LGN
 Striate cortex
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VISUAL ADAPTATION

• Light adaptation: Retina adapting to bright light

Very quick

Merely disappearance of Dark Adaptation

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Dark adaptation curve

Visual threshold falls progressively

Initial small curve

• represents the adaptation of cones

Remainder of the curve

• represents adaptation of rods
Night Blindness
• Mild cases of Vitamin A deficiency lead to a
slowing of S2 component of the dark
adaptation, yet without any alteration in the fully
dark adapted visual threshold
• Why?
Because all the bleached opsin is able to combine
with retinoid, the recombination is simply
slowed.
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• 1 minute : 10 x sensitivite

• 20 minute : 6000 x sensitive

• 40 minute : 25000 x sensitive

• When fully dark adapted, the retina is about

one lakh times more sensitive to light than
when bleached
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Mechanism
• Visual pigment mechanism
• Other mechanisms
• - Change in pupil size
• - Neural adaptation
Feedback inhibition

Lies within the neuron itself

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What are the Factors that prolong dark

adaptation ?
 Vitamin A deficiency
 Age related maculopathy
 Anoxia
 Tobacco
 Anaesthesia
 Opacities in the ocular media
 Retinal degeneration
 Myopia
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• Delayed dark adaptation

occurs in diseases of rods
e.g., vitamin A deficiency &
retinitis pigmentosa

Oguchi’s disease:
• prolonged rod dark adaptation
• Despite normal rhodopsin
regeneration
• Demonstrate neural mechanism of
dark adaptation
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References
Adler’s Physiology Of The Eye – 11th Edition
Anatomy And Physiology Of Eye - 2nd Edition- A. K
Khurana
Yanoff & Duker Ophthalmology - 4h Edition
Clinical Ophthalmology - 8th Edition- J. Kanski
AAO Retina and Vitreous - Section 12
AAO Fundamentals and Principles of Ophthalmology -
Section 2
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