L21 Retinal Pigment Physiology

What cell absorbs light that is focused on the macula and not used by photoreceptors?

absorbed by melanosomes of the RPE

What structure dissipates heat from light focused on the macula?

choroid vasculature dissipates this heat

How do RPE cells prevent photo-oxidative damage?

RPE cells contain antioxidants to neutralize ROS and have a high capacity for cell repair

melanosomes

absorbs light/heat and prevents light reflection back to photoreceptors

tyrosinase is a key enzyme in this structure to produce melanin

Mutations in what gene can lead to albinism?

tyrosinase because it is a key enzyme that is used to produce melanin

How does ocular albinism disrupt binocular vision?

there is improper routing of ganglion cells through the optic chiasm

fewer ipsilateral projections of RGC axons

fovea fails to develop in eyes without melanosomes

How do essential nutrients get to the RPE from the outer retina?

active transport

GLUT1 and GLUT3 transport glucose and sensitive to O2 levels

How is glucose affected by glucose transport?

reduced O2: more GLUT transport

more O2: less GLUT transport

regulated by HIF-1

What do RPE mostly use for energy?

RPE cells utilize lactate for energy and transport most glucose

How does RPE participate in water and ion transport?

RPE transcellulary transports ions from the sub retinal space, through the RPE cytoplasm, and out through the basolateral membrane

*transport of chloride ions are the main driving force

How do RPE cells transport lactic acid?

across RPE from apical side (photoreceptor) to basolateral side (choroidal side)

utilizes NKA, NHE, MCT

Docosahexaenoic acid

polyunsaturated omega-3 fatty acid that is synthesized in the liver and transported to the RPE through the blood

essential for the renewal process of photoreceptor outer segment membranes and efficient phototransduction

Which enzyme mediates RPE uptake of vitamin A or all-trans retinol?

STRA6, a transmembrane protein expressed in RPE

What does disruption of the STRA6 gene in humans result in?

minor vision problems to anopthalmia

visual cycle

process that photoreceptors and RPE use to convert all-trans-retinal to 11-cis-retinal

*rods lack the ability for this conversion

What is the key enzyme of the visual cycle?

retinol dehydrogenase

rod vision cycle

1. 11-cis retinal is converted to all-trans retinal by light

2. all-trans retinal converted to all-trans retinol in outer segment

3. all trans retinol transported to RPE vis IBRP

4. all-trans retinol converted to 11-cis retinol in RPE

5. 11-cis retinol converted to 11-cis retinal in RPE

6. 11-cis retinal is delivered back to outer segment via IRBP

What cells are involved in the cone visual cycle?

retinal cells and RPE cells

Where do cones receive 11-cis retinal from?

RPE

Where do cones receive 11-cis retinol from?

Muller cells

T/F: cones can convert 11-cis retinol to 11-cis retinal

true

Why are there differences between the cone and rod visual cycle?

higher cone demand

competition with rod visual cycle

larger distance between RPE and cones vs. rods

Why is lipofuscin accumulated in RPE cells ?

lipofuscin is composed of incomplete degradation of internalized macromolecules from visual cycle

this accumulate with age and melanosomes migrate basally to associate with lipofuscin

there presence is strongly correlated with cellular dysfunction and contributes to retinal aging and degeneration (AMD)

A2E

component of lipofuscin

source of autofluorescence in fungus autofluroescence

build up with time and are normally increased with aging

A2E-epoxides

formed by A2E exposure to blue light

damage DNA

leads to RPE cell death

RPE death leads to photoreceptor death

retinitis pigmentosa

d/t mutation in rhodopsin gene

destabilizes protein and there is reduced function and transport which leads to photoreceptor cell death

Stargardt's Macular Degeneration

due to the accumulation of fluorescent lipofuscin pigments in RPE cells, RPE degeneration, photoreceptor

d/t mutation in ABCA4 mutation that encodes disk membrane protein required for visual cycle

Leber's Kongenital amaurosis

caused by mutations in RPE65, which encodes a RPE protein required for rod visual cycle

T/F: RPE cells phagocytose photoreceptor outer segments

true

RPE drusen

extracellular lipid deposits that are derived from remnants of RPE phagocytosis of photoreceptors

Where are RPE drusen located?

between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane

hard drusen

does not usually affect vision

soft drusen

increases risk of age-related macular degeneration

age-related macular degeneration

damage/reduced RPE function leads to insufficient photoreceptor support

leads to photoreceptor death

Dry AMD

early-intermediate

fuzzy/distorted vision

advanced: loss of RPE in macular region leads to loss of photoreceptors and causes central vision loss

Wet AMD

advanced neovascular stage

growth of choroidal vasculature into normally avascular sub-RPE and sub-retinal regions

loss of more RPE/photoreceptors/central vision