Biochemistry and Metabolism- Retina

Question 1

What tissue has the highest oxygen consumption in the human body

Answer 1

The retina has the highest rate of oxygen consumption of any tissue in the human body because of its high metabolic activity

Question 2

What is the process which converts light energy into electrical impulse

Answer 2

phototransduction

Question 3

How does the RPE and Neurosensory retina form

Answer 3

These laminar structures arise from an invagination of the embryonic optic cup that folds the neuroectodermal layer into apex­to­apex contact with itself, creating the subretinal space

Question 4

What cells does the neural retina compose of

Answer 4

• photoreceptors (rods and 3 types of cones)
• bipolar cells (rod on­bipolar cells and cone on­ and off­bipolar cells)
• interneurons (horizontal and amacrine cells)
• ganglion cells and their axons, which form the retinal nerve fiber layer and the optic
  nerve
• glial cells, including astrocytes, Müller cells, and microglia

Question 5

Are rods more sensitive than cones or the other way round

Answer 5

Rods are highly sensitive and can be stimulated by a single photon. Cones are less sensitive than rods, but they can adapt to a wider range of light intensities and respond more rapidly to repetitive stimulation

Question 6

How many discs and rhodopsin molecules are found in the rod

Answer 6

There are approximately 1000 discs within a rod outer segment and 1 million membrane­ bound rhodopsin molecules in each disc

Question 7

What do the discs of the rod do

Answer 7

contain the protein machinery to capture and amplify light energy

Question 8

How many helical loops is the rhodopsin molecule made of

Answer 8

is a freely diffusible membrane protein with 7 helical loops that is embed­ded in the lipid membrane

Question 9

What is the relation of rhodopsin to different colours of light

Answer 9

absorbs green light best at wavelengths of approximately 510 nm. It absorbs blue and yellow light less well and is insensitive to longer wavelengths (red light)

Question 10

What is the function of the plasma membrane on the outer segment of the rod

Answer 10

contains the cationic cyclic nucleotide– gated (CNG) channels, which are gated by cyclic guanosine monophosphate (cGMP). This channel controls the flow of sodium (Na+) and calcium (Ca2+) ions into the outer segment

Question 11

Where is the rhodopsin molecule located

Answer 11

embedded in the lipid membrane of the outer segment with 7 helical loops

Question 12

Is the rod molecule depolarized in the dark or light

Answer 12

Dark by constant inflow of sodium and calcium ions into the outer segment

Question 13

What happens when light activates the rhodopsin

Answer 13

hyperpolarization of the photoreceptor’s membrane potential. Once rhodopsin absorbs a quan­tum of light, the 11­cis double bond of retinal is reconfigured (creating all­trans­retinal, also called all­trans­retinaldehyde) and the opsin molecule undergoes a series of rapid configurational changes to an activated state known as metarhodopsin II. Light­activated rhodopsin triggers a second molecule, transducin, by causing an exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP)

Question 14

How many transducin molecules can one rhodopsin activate

Answer 14

100

Question 15

What does activated transducin do

Answer 15

excites a third protein, cGMP phosphodiesterase (PDE), which hydrolyzes cGMP to 5′­noncyclic GMP. The decrease in cGMP closes the CNG channels, which stops entry of Na+ and Ca2+ and hyperpolarizes the rod. Hyperpolarization stops the release of glutamate from the synaptic terminal

Question 16

How does the CNG channels open once light is extinguished

Answer 16

active components of the phototransduction cascade be fully quenched and cGMP resynthesized to allow open­ing of the CNG channels

Question 17

How is rhodopsin inactivated

Answer 17

by phosphorylation at its C­ terminal end by rhodopsin kinase and subsequent binding to arrestin. Inactivation of rhodopsin is aided by recoverin, a highly conserved Ca2+­binding protein found in both rods and cones.

Question 18

How is transducin inactivated

Answer 18

hydrolysis of GTP to GDP via transdu­cin’s intrinsic GTPase activity, which reduces PDE activity.

Question 19

How are the discs in the rod different to the ones found in the cones

Answer 19

they are disconnected from the outer plasma membrane

Question 20

Which rim proteins are found in rods

Answer 20

peripherin and rod outer segment protein 1 (ROM1), which play a role in the development and maintenance of the disc’s curvature. Peripherin and ROM1 are also found in cone outer segments. Another protein in rod discs is ABCA4, an ATP­binding cassette (ABC) transporter

Question 21

What is the function of ABCA4 transporter

Answer 21

energy­ dependent transport of substrates from the disc lumen to the rod cytosol.

Question 22

Which rim protein is exclusively found in rods and not cones

Answer 22

ABCA4 is unique to rod discs and is not found in cones. It functions as a transporter of all­trans­retinal.

Question 23

Which segment (inner or outer) contains mitochondria

Answer 23

Inner

Question 24

What is the impact on a person who is born without cones

Answer 24

A person without cones loses the ability to read and see colors and can be legally blind. In comparison, lost rod function is a less severe visual problem, except under sco­topic conditions.

Question 25

What is flicker fusion threshold

Answer 25

the frequency of a repetitive stimulus at which it appears to be a completely steady light stimulus

Question 26

What is the flicker fusion threshold in rods vs cones

Answer 26

This threshold is much higher in cones (approximately 100 Hz) than in rods (approximately 30 Hz)

Question 27

What spectral classes of cones do humans have

Answer 27

• short­wavelength­sensitive cones (termed Scones),which detect only color by comparing their signals with those of the M cones; this mechanism creates blue­ yellow color vision
• middle ­wavelength sensitive cones (termed M cones), which detect high ­resolution achromatic (black and white) contrast
• long ­wavelength sensitive cones (termed L cones), which evolved in primates to enhance color vision; this mechanism creates red­green color vision

Question 28

Which type of cone is the fewest

Answer 28

Both L and M cones contribute to achromatic and chromatic contrast. Therefore, both are more numerous than S cones in the human retina

Question 29

What is the most common Rhodopsin gene (RHO) mutation

Answer 29

P23H (responsible for 10% of RP cases in the United States) which causes the rhodopsin protein not to fold properly and instead to accumulate in the rough endoplasmic reticulum

Question 30

Impact of rod transducin protein mutation

Answer 30

a dominant mutation in the GNAT1 gene causes congenital stationary night blindness, Nougaret type, the oldest-known form of aD stationary nyctalopia. transducin becomes continuously activated, an example of constitutively active rods that do not degenerate.

Question 31

Impact of rod cGMp phosphodiesterase mutation

Answer 31

Defects in either the α-subunit (pDea) or β-subunit (pDeB) of cGMp phosphodiesterase (rod pDe) cause arrp

Question 32

Impact of rod cGMp–gated channel mutation

Answer 32

Null mutations of the rod cGMp–gated channel β-subunit cause arrp

Question 33

Impact of arrestin, rhodopsin kinase mutation

Answer 33

a mutation either in the gene SAG (2q37), which encodes arrestin, or in GRK1 (13q34), which encodes rhodopsin kinase, causes Oguchi disease, a form of stationary nyctalopia.

Question 34

Impact of Guanylate cyclase gene mutation

Answer 34

Null mutations of the guanylate cyclase gene cause LCA, a childhood AR form of RP. LCA shows genetic heterogeneity.

Question 35

Impact of rod ABC transporter mutation

Answer 35

Mutations in the ABCA4 gene cause recessive defects of ABC transporter proteins, which cause Stargardt disease.

Question 36

Impact of Cone cGMp–gated channel mutation

Answer 36

a homozygous defect in the cone cGMp–gated channel α-subunit causes achromatopsia, loss of all cone function.

Question 37

Impact of L- and M-cone opsins mutation

Answer 37

Mutations in the genes coding for L- and M-cone opsins cause defects that lead to S-cone (or blue-cone) monochromatism. these defects occur only in males because of the gene’s location on the X chromosome. Defects in all 3 cone opsins lead to achromatopsia, also known as rod monochromatism.

Question 38

Impact of L- or M-cone opsins mutation

Answer 38

Defects in one or the other of the X-linked L- or M-cone opsin genes cause red-green color deficiencies, almost exclusively in males

Question 39

What types of cells are found in the retina

Answer 39

• neurons (photoreceptor, bipolar, horizontal, amacrine, and ganglion cells)
• glial cells (Müller cells, astrocytes, microglia)
• vascular cells (endothelial cells and pericytes)

Question 40

How does information flow from photoreceptors to optic nerve

Answer 40

3­ neuron chain. photoreceptor cell to bipolar cell to ganglion cell. Horizontal cells and amacrine cells are interneurons that regulate the flow of information. Glial cells and vas­cular elements support the neuronal components.

Question 41

How many types of cone and rod bipolar cells are present

Answer 41

9–12 different kinds of cone bipolar cells but only 1 type of rod bipolar cell

Question 42

What are the two types of bipolar cells

Answer 42

on-bipolar and off-bipolar cells

Question 43

What kind of bipolar cell is present in the fovea

Answer 43

a cone has midget bipolar cells contacting only a single cone, and usually a single ganglion cell, for high spatial acuity

Question 44

Which photoreceptors are not involved in high spatial resolution

Answer 44

Rods and probably S cones have only on­bipolar cells. Thus, neither rods nor S cones are involved in high spatial resolution. S cones are involved in color vision; rods, in dim light (night vision).

Question 45

What is the function of horizontal cells

Answer 45

antagonistic interneurons that provide negative feedback to photoreceptors. The dendrites of horizontal cells synapse with cones

Question 46

What is the function of amacrine cells

Answer 46

Like horizontal cells, amacrine cells are inhibitory interneurons. Cone amacrine cells mediate antagonistic interactions among on­bipolar, off­bipolar, and ganglion cells. Rod bipolar cells do not usually synapse directly with ganglion cells but rather send their signal to amacrine cells, which then deliver the signal to on­ and off ­bipolar ganglion cells. Thus, rod signals undergo additional synaptic delays before they reach the ganglion cell output.

Question 47

Types of ganglion cells

Answer 47

1) tonic cells driven by L or M cones; (2) tonic cells driven by S cones; and (3) phasic cells

Question 48

Function of the tonic ganglion cells

Answer 48

transmits signals from the cones that are relatively well maintained for the duration of the light or dark stimulus

Question 49

Function of phasic gangion cells

Answer 49

transmits signals at the beginning or end of a light stimulus, producing a brief or transient response

Question 50

Function of muller cells

Answer 50

glial in origin and form a supporting element in the neural retina extend­ ing from the inner segments of the photoreceptors to the internal limiting membrane (ILM), which is formed by their end feet. They buffer the ionic concentrations in the extracellular space, enclose the subretinal space by helping form the external limiting membrane (ELM), and may play a role in vitamin A metabolism of cones.

Question 51

Functions of macroglia (astrocytes)

Answer 51

physical support to neuronal and vascular cells. Participate in blood retinal barrier. Form myelin sheath of optic nerve. Guide neuronal migration during development and exchange metabolites with neurones

Question 52

Functions of microglia

Answer 52

Microglia are related to tissue macrophages and are activated when retinal homeo­stasis is disturbed. These cells mediate immune responses in the central nervous system

Question 53

Function of pericytes

Answer 53

Pericytes surround the endothelial cells and are modified smooth muscle cells that play a role in autoregulation of retinal blood vessels. Endothelial cells form the blood–retina barrier; pericytes structurally support the endothelium and sup­ press proliferation, loss of which leads to increased permeability and development of microaneurysms.