Biochemistry and Metabolism- Retina Flashcards
What tissue has the highest oxygen consumption in the human body
The retina has the highest rate of oxygen consumption of any tissue in the human body because of its high metabolic activity
What is the process which converts light energy into electrical impulse
phototransduction
How does the RPE and Neurosensory retina form
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
What cells does the neural retina compose of
- 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
Are rods more sensitive than cones or the other way round
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
How many discs and rhodopsin molecules are found in the rod
There are approximately 1000 discs within a rod outer segment and 1 million membrane bound rhodopsin molecules in each disc
What do the discs of the rod do
contain the protein machinery to capture and amplify light energy
How many helical loops is the rhodopsin molecule made of
is a freely diffusible membrane protein with 7 helical loops that is embedded in the lipid membrane
What is the relation of rhodopsin to different colours of light
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)
What is the function of the plasma membrane on the outer segment of the rod
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
Where is the rhodopsin molecule located
embedded in the lipid membrane of the outer segment with 7 helical loops
Is the rod molecule depolarized in the dark or light
Dark by constant inflow of sodium and calcium ions into the outer segment
What happens when light activates the rhodopsin
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)
How many transducin molecules can one rhodopsin activate
100
What does activated transducin do
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
How does the CNG channels open once light is extinguished
active components of the phototransduction cascade be fully quenched and cGMP resynthesized to allow opening of the CNG channels
How is rhodopsin inactivated
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.
How is transducin inactivated
hydrolysis of GTP to GDP via transducin’s intrinsic GTPase activity, which reduces PDE activity.
How are the discs in the rod different to the ones found in the cones
they are disconnected from the outer plasma membrane
Which rim proteins are found in rods
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
What is the function of ABCA4 transporter
energy dependent transport of substrates from the disc lumen to the rod cytosol.
Which rim protein is exclusively found in rods and not cones
ABCA4 is unique to rod discs and is not found in cones. It functions as a transporter of alltransretinal.
Which segment (inner or outer) contains mitochondria
Inner
What is the impact on a person who is born without cones
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.
What is flicker fusion threshold
the frequency of a repetitive stimulus at which it appears to be a completely steady light stimulus
What is the flicker fusion threshold in rods vs cones
This threshold is much higher in cones (approximately 100 Hz) than in rods (approximately 30 Hz)
What spectral classes of cones do humans have
- 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
Which type of cone is the fewest
Both L and M cones contribute to achromatic and chromatic contrast. Therefore, both are more numerous than S cones in the human retina
What is the most common Rhodopsin gene (RHO) mutation
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
Impact of rod transducin protein mutation
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.
Impact of rod cGMp phosphodiesterase mutation
Defects in either the α-subunit (pDea) or β-subunit (pDeB) of cGMp phosphodiesterase (rod pDe) cause arrp
Impact of rod cGMp–gated channel mutation
Null mutations of the rod cGMp–gated channel β-subunit cause arrp
Impact of arrestin, rhodopsin kinase mutation
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.
Impact of Guanylate cyclase gene mutation
Null mutations of the guanylate cyclase gene cause LCA, a childhood AR form of RP. LCA shows genetic heterogeneity.
Impact of rod ABC transporter mutation
Mutations in the ABCA4 gene cause recessive defects of ABC transporter proteins, which cause Stargardt disease.
Impact of Cone cGMp–gated channel mutation
a homozygous defect in the cone cGMp–gated channel α-subunit causes achromatopsia, loss of all cone function.
Impact of L- and M-cone opsins mutation
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.
Impact of L- or M-cone opsins mutation
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
What types of cells are found in the retina
- neurons (photoreceptor, bipolar, horizontal, amacrine, and ganglion cells)
- glial cells (Müller cells, astrocytes, microglia)
- vascular cells (endothelial cells and pericytes)
How does information flow from photoreceptors to optic nerve
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.
How many types of cone and rod bipolar cells are present
9–12 different kinds of cone bipolar cells but only 1 type of rod bipolar cell
What are the two types of bipolar cells
on-bipolar and off-bipolar cells
What kind of bipolar cell is present in the fovea
a cone has midget bipolar cells contacting only a single cone, and usually a single ganglion cell, for high spatial acuity
Which photoreceptors are not involved in high spatial resolution
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).
What is the function of horizontal cells
antagonistic interneurons that provide negative feedback to photoreceptors. The dendrites of horizontal cells synapse with cones
What is the function of amacrine cells
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.
Types of ganglion cells
1) tonic cells driven by L or M cones; (2) tonic cells driven by S cones; and (3) phasic cells
Function of the tonic ganglion cells
transmits signals from the cones that are relatively well maintained for the duration of the light or dark stimulus
Function of phasic gangion cells
transmits signals at the beginning or end of a light stimulus, producing a brief or transient response
Function of muller cells
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.
Functions of macroglia (astrocytes)
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
Functions of microglia
Microglia are related to tissue macrophages and are activated when retinal homeostasis is disturbed. These cells mediate immune responses in the central nervous system
Function of pericytes
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.
