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To enable vision, photoreceptors in the retina make
synaptic contacts with their partners called "ON bipolar neurons" and transmit info to the brain
The retina is an extension of the ________
central nervous system (CNS)
Where does the retina originate from?
Developing brain (diencephalon)
Where do the retina's axons originate from?
Optic nerve, which is a CNS structure that projects info to the brain
Lateral Retinal Pathway
refers to the horizontal connections within the retina, facilitated by cells like horizontal and amacrine cells, which allow signals to spread laterally
Cells involved in the lateral pathway
Amacrine
Horizontal
Vertical Retinal Pathway
describes the flow of visual information from photoreceptors (rods and cones) to bipolar cells, and then to retinal ganglion cells (RGCs), ultimately transmitting signals to the brain.
Cells involved in the Vertical Pathway
Photoreceptors
Bipolar cells
Retinal ganglion cells
Light sensitive cells in the retina
Photoreceptors
2 types of photoreceptors
Rods and cones
Responsible for low-light-level sensing, enabling scotopic vision (night vision)
Rods
Responsible for high-light-level sensing, enabling photopic vision (day vision)
Cones
Compare the number of photopigments in the photoreceptors
Rod cells have more photopigments (there are 100x more rods than cones)
Compare the amplification shown in rods vs. cones
-Rods show more
-Cones show less
Which type of photoreceptor shows directional selectiveness?
Cones
Which type of photoreceptor have a high sensitivity?
Rods (due to low light)
Which type of photoreceptor has a low sensitivity?
Cones
Rods have a (high/less) convergent retinal pathway?
High
Cones have a (high/less) convergent retinal pathway?
Less
Which type of photoreceptor has a slow response?
Rods
Which type of photoreceptor shows a fast response?
Cones
Photoreceptor that shows a slow acuity
Rods
Photoreceptor that shows a high acuity, especially in the macula
Cones
How many pigment types do rods have?
One
How many pigment types do cones have?
Three (SML)
The visual pigment in the rod cells is
Rhodopsin
The visual pigment in the cone cells is
Lodopsin
What type of tissue does the retinal pigment epithelium (RPE) have?
Simple cuboidal epithelium
What type of pigment is found in the RPE and what is its function?
Melanin- absorbs excess light to reduce scatter
How does the retinal pigment epithelium (RPE) contribute to the blood-retinal barrier?
The RPE forms the outer blood-retinal barrier through tight junctions composed of occludin and claudin
The tight junctions in the RPE, which include occludin and claudin, are part of the _________.
zonula occludens
Which structure in the eye has the highest melanin density?
Macula (increases visual acuity)
The RPE provides nutrition for the _______.
neuroretina
The RPE is also responsible for:
phagocytosis of waste or degraded materials
What is the fundamental role of the RPE?
Maintain the health of the neural retina and choriocapillaris
What structures connect RPE cells, forming the blood-retinal barrier?
Zonula occludens
What is the function of the blood-retinal barrier formed by the RPE?
Efficient isolation of the inner retina from systemic influences at the choroidal side
The blood retinal barrier is of importance for (2)?
-Immune privilege of the eye
-Selective transport between the blood and subretinal space
How does the RPE control nutrient and waste exchange?
The RPE selectively regulates the movement of nutrients and metabolites from the choriocapillaris into the retina while efficiently removing waste products
Normal pH of the retina =
7.28
Water is eliminated from the subretinal space via
active transport by the RPE Aquaporins
In the RPE cells, ion movement occurs by (4):
1) Na+/K+ ATPase pumps
2) Na+/K+/Cl- and Na+/2HCO3- cotransporters
3) Cl-/2HCO3- exchangers
4) Gated and undated ion channels
Moves a significant amount of lactate (a product of anaerobic metabolism) across the RPE
Proton-lactate water cotransporter
Lactate is a product of ________.
anaerobic metabolism
In the RPE cells, water passage occurs through
aquaporins
In the RPE cells, glucose passage occurs through
glucose transporters (GLUT1)
Where are glucose transporters located?
in both apical and basal membrane
Function of the glucose transporters
Maintain steady supply of glucose to the active photoreceptors
2 families of glucose transporters
1) Faciliatated diffusion glucose transporter family (GLUT family) - primarily GLUT1
2) Na+ dependent glucose transporter one (SGLT family)
What does the RPE do with photoreceptor outer segment discs?
The RPE phagocytoses fragments from the continuous shedding of photoreceptor outer segment discs
How many discs does the RPE phagocyotose daily?
2000 discs daily
Undigested material in the RPE cells accumulates as
lipofuscin
Lipofuscin
yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion
A2E stands for
N-retinylidene-N-retinylethanolamine
In which substance has A2E been identified?
lipofuscin
How does A2E substance affect RPE cells?
It impairs degradation in RPE cells, causing accumulation and inducing cell death
What condition is associated with the accumulation of A2E in the RPE cells?
ARMD
RPE metabolizes and stores ________.
vitamin A
Why is it important for the RPE to metabolize and store vitamin A?
Converting retinol --> retinyl esters for storage, and then back to 11-cis-retinal for use in photoreceptors
Vitamin A is also called
all-trans-retinol
Why is vitamin A important in the rod disc renewal system?
Vitamin A, in the form of 11-cis-retinal, is essential in the rod disc renewal system as it helps regenerate rhodopsin for proper rod function, particularly in night vision.
What is the precursor of rhodopsin pigment and how does it help vision?
11-cis-retinal; helps in night vision
LRAT =
Lecithin Retinol Acyltransferase
What does LRAT do in the retina?
helps store vitamin A in the form of retinyl esters in the RPE.
RPE65 =
Retinoid isomerohydrolase
What does RPE65 do in the retina?
helps convert vitamin A (all-trans-retinol) into 11-cis-retinal
RPE cells contribute to the formation of the
IPM (interphotoreceptor matrix) between the RPE and photoreceptors
What is IPM formed by in the retina?
Hyaluronan (HA), a type of glycosaminoglycan
Hyaluronan is binded to (2)
-Apical RPE by RHAMM
-Müller cells by CD44
A derivative of vitamin A that is administered as a multi-vitamin tablet, to preserve the retina layers and slow ARMD progression
Areds-2
RPE produces ________ that drive certain cellular processes.
growth factors
Which growth factors are produced by the RPE?
-Angiogenic Factor (VEGF)
-Anti-angiogenic Factor (PEDF)
Angiogenic Factor (VEGF) maintains the function of the ________.
choriocapillaris
Oveproduction of VEGF results in
neovascularization (leading to vision loss due to leaking blood vessels and fluid buildup in the retina)
Name of the anti-angiogenic factor
Pigmented epithelium-derived factor (PEDF)
PEDF acts as a:
Homeostatic factor- by inhibiting abnormal blood vessel growth (neovascularization)
PEDF is aka
serpin F1
PEDF is a multifunctional protein with the following functions (3):
1) anti-angiogenic
2) anti-tumorigenic
3) neutrotrophic
How much VEGF and PEDF should be present in the retina?
PEDF secretion should be higher than VEGF
What is an imbalance between the growth factors, particularly a decrease in PEDF, implicated to?
Development of conditions such as ARMD and choroidal neovascularization (CNV)
Structures within the RPE cells that absorb light
Pigment granules
Role of the pigment granules
Reduce excess light scatter
What is the relationship between the RPE and photoreceptors?
Is reciprocal—both layers depend on each other, and dysfunction in one affects the other
How do retinal degenerative diseases and dystrophies affect the RPE?
Cause changes in the RPE that are clinically visible