Chapter 13: RPE

Question 1

What is the Retinal Pigment Epithelium (RPE)?

Answer 1

a single layer of cuboidal epithelial cells that constitutes the outermost layer of the retina, located b/w the choriocapillaris and the photoreceptor outer segments

Question 2

How many cells are located in the RPE layer? What is the ratio of RPE cells to photoreceptors?

Answer 2

4-6 x 10^6 RPE cells/eye

45:1 ratio of photoreceptors: RPE cells

Question 3

Embyrologically, what is the RPE derived from?

Answer 3

Derived from the optic cup (same as neural retina), but differentiates into secretory epithelium

Question 4

Describe the anatomy of the RPE cell

Answer 4

• RPE are polarized epithelial cells, with long microvillous processes on their apical surface that interdigitate with outer segments of photoreceptors.
• On their basal surface there are many infoldings, which serve to increase surface area for solute exchange
• Joined near their apical sides via tight junctions, which constitutes the outer blood-retina barrier
• In addition to organelles, contain phagosomes, peroxisomes and melanin (suggest active in detoxifying radicals and oxidized lipids)

Question 5

How does the RPE produce energy?

Answer 5

Produces energy via the TCA cycle, glycolysis, and pentose phosphate pathway

Question 6

What is the primary carbon source for the RPE? Secondary sources?

Answer 6

Primary source= glucose

Other sources: glucosamine, fucose, galactose, mannose

Question 7

What component of the RPE accounts for > 80% of its wet weight?

Answer 7

Water

Question 8

What is RPE Na+K+ATPase? why is it important?

Answer 8

located on the apical surface rather than the basal surface (different than orientation in most cells) and functions to maintain the balance of Na+ and K+ in the subretinal space

Question 9

What is RPE65?

Answer 9

a protein unique to the RPE, is an obligate component of the isomerization and hydrolysis of vitamin A

Question 10

What percentage of the wet weight of the RPE is derived from lipids?

Answer 10

3%; 50% of which are phospholipids, >80% of which are phosphatidylcholine and phosphatidylethanolamine

Question 11

What is the function of saturated fatty acids in the RPE?

Answer 11

used for retinol esterification and enegy metabolism by the RPE mitochondria

Question 12

What are the functions of the RPE?

Answer 12

• Visual Pigment Regeneration
• Phagocytosis of shed photoreceptor outer segment discs
• Transport
• Pigmentation
• Retinal Adhesion

Question 13

How does the concentration of vitamin A in the RPE compare to other tissues in the body?

Answer 13

Has the second highest vitamin A concentration in the body (second to the Liver)

Question 14

What is the basic function of the RPE in the visual process?

Answer 14

generation of 11-cis-retinaldehyde (used in formation of rhodopsin)

Question 15

What molecules are used to create rhodopsin?

Answer 15

Opsin (synthesized by photorecepter) + 11-cis-retinaldehyde

Question 16

What happens to rhodopsin when it becomes photolyzed?

Answer 16

Isomerizes to 11-trans-retinaldehyde, which is released, converted to all-trans-retinol via retinal dehydrogenase, returned to the RPE via interphotoreceptor retinoid binding protein (IRBP), where it is converted into retinol ester for storage.

When needed for rhodopsin regeneration, is converted to 11-cis-retinol–>11-cis-retinal and returned to the photoreceptor via the IRBP

Question 17

How does the RPE acquire vitamin A?

Answer 17

1- through release during bleaching of rhodopsin and return via regeneration of visual cycle
2- from circulation
3- via phagocytosis of shed photoreceptor outer disc segments

Question 18

Why does the RPE store retinoids as esters?

Answer 18

Stores retinoids as esters b/c the alcohol and aldehyde formations are membranolytic

Question 19

What happens to photoreceptor outer disc segments?

Answer 19

They are encapsulated in phagosomes, which fuse with lysozymes and are digested.

Building blocks are then recycled into photoreceptors for use in synthesis and assembly of new discs

Question 20

Where does lipofuscin in the RPE come from?

Answer 20

derived from digested photoreceptor disc membranes

is responsible for generating the signal during fundus autofluorescence imaging

Question 21

How many discs does each photoreceptor outer segment shed each day? How many discs does each RPE digest per day?

Answer 21

Outer segments shed approx. 100 discs/day

RPE digests >4000 discs per day

Question 22

What kind of a pattern for disc shedding do the photoreceptors follow?

Answer 22

They follow a circadian rhythm
Cones- shed most vigorously at onset of darkness
Rods- shed most vigorously within 2 hrs of light onset

Question 23

How does dopamine interact with photoreceptors?

Answer 23

Dopamine acts on the photoreceptor-RPE complex to control disc shedding

Question 24

What direction does Na+ flow through the RPE? K+?

Answer 24

Na+ is actively transported from the choriocapillaris to the subretinal space, while K is transported out of the RPE

Question 25

Where does active HCO3 transport occur on the RPE?

Answer 25

On the apical surface, similar to Na+K+ATPase

Question 26

What is the basis for the Electro-Oculogram?

Answer 26

the Trans-RPE potential is the basis for the EOG, which is the most common electrophysiologic test for evaluating the RPE

Question 27

Where is the melanin in the RPE located?

Answer 27

Melanin is found predominantly in the apical and mid-portions

Question 28

Why does the fundus in older people appear less pigmented than in younger people?

Answer 28

B/c as humans age, melanin granules fuse with lysozymes

Question 29

What is the role of melanin in the RPE?

Answer 29

Exact mechanism is unknown, but there is speculation

May act as a neural-density filter to decrease light scatter
Though to play a role in development (when melanin is below a critical level, aberrant neuronal migration in the visual pathway, lack of foveal development, low vision, nystagmus, and strabismus have been shown to occur)

Question 30

How does the retina adhere to the RPE?

Answer 30

• passive hydrostatic forces
• interdigitation of RPE and photoreceptor outer segments
• active transport of SRF
• complex structure and binding properties of interphotorecepter matrix