Biochemistry of Vision Flashcards
The _____ is a small depression in the retina where visual acuity is the highest, it is where the retinal ____ are particularly concentrated
Fovea; cones
Function of pigmented epithelial cells
Filled with melanin so that residual light is absorbed — doesn’t pass into surrounding cells
Where are pigmented epithelial cells located
Outside nerual retina and attached to choroid layer
Axons of ____ cells form the optic nerve
Ganglion
What cells allow horizontal processing of light?
Horizontal cells
Amacrine cells
The signal transduction pathway of light—>vision originates from a _____ system
Rhodopsin is made up of the receptor ______ and the _______ (retinal) to which it is covalently bound
GPCR
Opsin; chromophore
What is the G protein associated with the Rhodopsin GPCR?
Transducin
What is the effector protein associated with the rhodopsin GPCR? What does it do?
PDE
Cleaves cGMP to GMP (GMP is second messenger)
What surface membrane protein is open in dark conditions, and contributes to partial depolarization in these dark conditions?
cGMP-gated channel
What surface membrane component recycles cGMP so that cells go back to depolarized state?
Guanylate cyclase
What ancillary protein functions in signal termination by blocking the interaction of rhodopsin with transducin?
B-arrestin
What enzyme phosphorylates rhodopsin, providing the first step in signal termination?
Rhodopsin kinase
Differentiate rods and cones in terms of sensitivity and spatial resolution
Rods = high sensitivity, low spatial resolution
Cones = low sensitivity, high spatial resolution
T/F: there is a high degree of turnover of photoreceptor cells
True; it is not a hospitable environment. Exposure to UV radiation, oxygenating species, and glucose
What area of the retina has phagocytosing ability
Retinal pigmented epithelium
In the dark, photoreceptor cells are ______and there are _____ neurotransmitters released
Depolarized; inhibitory
When the eyes are open, the photoreceptor cells are _________, which removes the _____ neurotransmitters typically released by default
Hyperpolarized; inhibitory
What makes rod cells unusual for excitable cells?
The membrane is partially depolarized at rest and hyperpolarizes upon stimulation
Partial depolarization of photoreceptor cells at rest means the NT _____ is continuously released.
_____ and _____ are the most common inhibitory neurotransmitters and as such inhibit the optic nerve bipolar cells
Glutamate
GABA; glycine
[note that glutamate is normally excitatory but in this case is inhibitory]
Hyperpolarization of photoreceptor cells stops ____ transmission and relieves the inhibition of the optic nerve bipolar cells
Glutamate
Rhodopsin is homologous to what type of receptor?
Beta-adrenergic receptor
[nerve cells in which epinephrine/NE acts as NT]
The retinal portion of rhodopsin is derived from _______
Vitamin A
The aldehyde of retinal forms a schiff base with the amine of ______, which when photoactivated becomes protonated
Lysine
Rhodopsin goes through several intermediate conformations of various names but the activated version is known as ________
Metarhodopsin II
cGMP PDE catalyzes what reaction with cGMP?
What effect does this have on the photoreceptor cell?
Hydrolysis of cGMP to 5’GMP
Lower concentration of cGMP causes hyperpolarization of visual cells —> visual signal transduction
Describe activation of transducin G protein
Light activates Gt —> which activates cGMP PDE —> catalyzes hydrolysis of cGMP to 5’GMP
Activation of rod photoreceptor:
Photon of light interacts with _____ in a photoreceptor cell, which then isomerizes to the all-trans configuration. This activates a _____ by conformational change in disk membrane.
Retinal; rhodopsin
Activated rhodopsin makes repeated contacts with _____ molecules, catalyzing its activation by release of GDP in exchange for cytoplasmic GTP
Transducin
[activated G protein binds inhibitory gamma subunits of PDE, activating its alpha and beta subunits]
Once PDE is activated, it hydrolyzes cGMP and the ____channels close which causes hyperpolarization due to ongoing efflux of ____ ions which cause voltage gated Ca channels to close
Sodium; potassium
Once hyperpolarization occurs, ______ _____ synthesizes cGMP, the second messenger in the cascade
Guanylyl cyclase
As the calcium level in the photoreceptor cell drops, the amount of _____ that is released also drops. This decrease causes ____ of the cell
Glutamate; depolarization
Role of calcium in dark conditions
In dark conditions, Ca and Na enter the rod OS through cGMP-gated ion channels
Calcium influx balances efflux through channel exchanger
Role of Ca in light conditions
Ca influx through cGMP channel stops but exchanger export continues (net loss of Ca)
This drop in intracellular Ca stimulates the activity of guanylate cyclase, restoring the [cGMP] and re-opens cGMP-gated ion channels
Signal termination begins with blockage of transducin. How is light-activated rhodopsin blocked from activating transducin?
Rhodopsin kinase phosphorylates COOH terminus of metarhodopsin II at Thr and Ser, allowing binding by arrestin and preventing interaction with transducin
The first step in signal termination is light-activated rhodopsin blockage from activating transducin. Next, there is rapid hydrolysis of ATP to ADP, causing dissociation of tranducin from _____ and reassociation of the beta and gamma subunits. Finally, elevated _____ levels re-open cGMP-gated ion channels (inhibitory) and ________ ______ synthesized cGMP from GTP
PDE; cGMP; guanylate cyclase
In light, low cGMP levels close ____ and ____ channels, reducing intacellular concentration of these ions.
During recovery, the low _____ levels induce recovery
Na; Ca
Ca
By controlling the rate of cGMP synthesis, ____ levels govern the rate by which the system is restored
Calcium
The purpose of the retinoid cycle is to regenerate what?
11-cis-retinal
While not a part of the neural retina, what layer is essential for normal function and survival of photoreceptors, existing in close proximity to the outer segments?
RPE cells
Principle enzymes for 11-cis-retinal regeneration in the visual cycle
What happens when this enzyme is dysfunctional?
RPE 65 (LRAT also important)
RPE 65 Dysfunction —> retinitis pigmentosa (loss of vision, pigment depositions, loss of periphery)
Events of retinoid cycle in the rod cell
Light-induced change from 11-cis to all-trans
Release of all-trans retinal from opsin
Enzymatic reduction of all-trans retinal to all-trans-retinol
Exportation of all-trans-retinol (with help of iRBP)
Events of retinoid cycle in retinal pigmented epithelium
All-trans-retinol uptake into RPE and translocation to ER
Esterification to all-trans-retinyl ester by LRAT
Conversion to 11-cis retinol
Oxidation from 11-cis retinol to 11-cis retinal
Exportation of 11-cis retinal
Once 11-cis retinal is regenerated in RPE and exported back to rod cell, it undergoes covalent attachment to ______ forming a functional _____
Opsin; rhodopsin
Cone receptors are homologues of _____
Rhodopsin
T/F: photoreceptor proteins are highly conserved evolutionarily
True
Rearrangements during DNA replication may lead to what complication of vision?
Loss of visual pigment genes — color blindness
Color blindness heritability
X-linked recessive
_____ is produced in the retina from vitamin A, from dietary beta carotene
_____ and _____ are used to maintain epithelial cells
Retinal
Retinol; retinoic acid
[retinol has hydroxyl group, retinoic acid has carboxyl group, retinal has aldehyde]
Consequences of vitamin A deficiency
Night blindness
Xeropthalmia
Keratinization of epithelium (GI, resp)
Dry, scaly skin
Vitamin A deficiency is the most important nutritional disorder with respect to the ______, characterized by Bitot spots, xerosis, and keratomalacia
Cornea
What are bitot spots
Build-uup of keratin superficially in conjunctiva. Usually oval, rectangular, or irregular in shape, “foamy” in appearance
Abnormal dryness of the conjunctiva and cornea of the eye, with inflammation and ridge formation
Xeropthalmia
Classifications: Night blindness Conjunctival xerosis Bitot spots Corneal xerosis Corneal ulceration/keratomalacia Corneal scar Xerophthalmic fundus
Non-visual presentations of Vit A deficiency
Growth impediment Poor wound healing Dry skin Follicular hpyerkeratosis Alopecia Bronchitis Pneumonia
Complications of excess vitamin A
Liver toxicity
Joint pain
Infants exposed to _____ in the womb may have birth defects like cleft palate and heart abnormalities
Isotretinoin
Nyctalopia
Night blindness; disorder of rod cells
Most often associated with vitamin A deficiency leading to insufficient rhodopsin
Xerosis
Metaplasia of conjunctival epithelium to stratified squamous type with keratinized surface
T/F: vitamin A plays an unknown role in maintaining specialized ocular epithelia; specifically loss of goblet cells
True
Macular degeneration is degeneration of what 2 components?
What are the effects?
RPE and retina
Results in loss of central field vision, poor night vision
complications: atrophy, macular hemorrhage, pigmentation, macular edema, subretinal fluid
_____ _____ like lutein and zeaxanthin play a direct role in the protection of the retina against damage with things like macular degeneration
Macular carotenoids (xanthophylls)
Mutations in what transporter are implicated in macular degeneration?
ABC4 (an ABC transporter that works in clearance of all trans retinal derivatives from photoreceptors)
Which two opsin proteins are x-linked?
Red
Green
