Biochemistry of the Visual System Flashcards
Photoreceptors Rod and Cone
Rods: Rhodopsin and detect light (no color)
High Sensitivity and low spatial resolution
MOST
Can respond to a single photon (retinal ganglion cell) ->Many Biopolar cells ->Many RODS
Cones: 3 Opsins (Red, Green, Blue)
Low sensitivity and high spatial resolution
One Retinal Ganglion Cell -> one bipolar cell-> one CONE
The outer segment membrane of the photoreceptors have Disc Membranes stacked inside and in these are:
GPCR System:
- Opsin [rhodompsin]
- Transducin (The G protein)
- cGMP Phosphodiesterase (effector protein)
The outer segment membrane has:
cGMP-gated Na+ channels
OPEN: dark , depolarized glutamate photoreceptor cell
CLOSE: light, hyperpolarized glutamate photoreceptor cell
Desensitization Proteins:
- B-Arrestin
- Rhodopsin
The 7TM Receptors
1/3 of all drug targets
Rhodompsin and opsin are examples
7TM protein
Opsin (Rhodopsin) Receptor
B-Adrenergic Receptors homologous
Lys296 (in the middle)+Retinal 11(VitA)= Schaffer base
LIGHT: isomerization causes rotation = 11-cis-retinal -> 11-trans-retinal
Light Absorption for Rhodopsin and the Cone receptors
Rod: 500nm. (3chr)
Blue: 420nm. (7chr)
Green: 530nm. (Xchr)
Red: 560nm. (XChr)
Signal Transduction: what happens in the membrane of the inner disc and the outer segment membrane
- Photon comes and causes isomerization from cis to trans, activating rhodompsin (meta-rhodompsin or Rh*)
- Meta- rhodopsin contacts the GDP-transducin =GTP-Transducin
- Causing cleavage of the a subunit of the transducin, which goes and contacts the cGMP Phosphodiesterase (PDE6) activating it
- cGMP->GMP hydrolysis
- Decreases cGMP (ligand to the Na+ channels on the outer segment membrane)
- Na+/Ca+ channel deactivated and Na+ channel closes
- Hyperpolarization
- Stop glutamate inhibitory NT release, cause in signal cascade to happen
Ca+ that comes in though the Na+ channel
Stops GC; so GTP does not become cGMP, and keeps channel closed
So when Ca+ is low due to closed channel, the GC is activated increasing cGMP and that opens the Na+/Ca+ channel
CA+2 controls the RATE at which the photoreceptors are desensitized and restored, by controlling the rate of cGMP synthesis
Amplification
One photon goes to one rhodopsin receptor
- > many G-protein transducins activated
- > many PDE6 activated
- > many GMP Made and many cation channels closed
- > membrane potential changes to 1mV and signal goes to brain
Signal Termination (Desensitization)
- Rh* blocked from activating Transducin
= Rhodopsin Kinase : phosphorylates Rh2* (GRK) at THR and SER or C-terminus, causing Arrestin to bind
=Transducin (GTPase) can’t bind to Rh* - GTP-> GDP causing the a-subunit to dissociate from the PDE6 back the b and y
- GC: decreased Ca+ causes GTP-> cGMP ,High cGMP open Na+ channels
Retinal vs Retinol and Retinoic acid
Retinal= vision protein for retina
Retinol and Retinoic Acid= for health of epithelial cells, cornea, and conjunctiva, t-cells, reproductive health
Vitamin A disorders
Effect the cornea Can cause XEROPHTHALMIA (dry eye syndrome): night blindness, conjunctival xerosis.... BITOT’S SPOTS: (keratin debris buildup in the conjunctiva): foamy in appearance Growth impairment Immune impairment Dry skin Lung problems Follicular Hyperkerarosis
EXCESS VIT A: liver toxicity and joint pain
VIT A when pregnant in the Accutane form = birth defects like cleft plate
Golden Rice
Rice that has genetically been engineered to have FORTIFIED B-CAROTENE which makes VIT A and grown in underserved countries
Beta-Carotene
->Rential -> Retinol
Foods with VIT A
- Carrots: night blindness
- Leafy greens : Xerophthalmia
- Sweet Potatoes: Keratinization of epithelium (GI + Resp)
- Squash: Dry Scaly skin
- Broccoli: AMD
6: Animal Products: Preventable blindness in children
Retinoic Cycle: how 11-cis-retinal is regenerated
STEP 1: In the Rod Cell
- 11-cis- retinal binds to opsin receptor
- Light changes the 11-cis to 11- trans
- Trans is released from the opsinthe and goes to the ABC transporter to leave the disc membrane inside the outer segment and enter its inside cytoplasm
- All trans- retinal -> all trans- retinol ( by aRDH: All Retinal Dehydrogenase)
- aRDH goes to REP (retinol pigmented epithelium) by the iRBP protein
Retinoic Cycle: how 11-cis-retinal is regenerated
STEP 2: In the retinal pigmented Epithelium (RPE)
- All- trans- retinol binds to CRBP (cellular retinoid binding protein)
- Esterification: to all- trans- retinyl ester (By LRAT)
- Conversion: to 11-cis- retinol + CRALBP (binding protein) (By RPE65)
- Oxidation: to 11-cis-retinal (By 11-cis- RDH)
- iRBP transports 11-cis-retinal to outer segment cytoplasm to disc membrane opsin
LRAT and RPE65 dysfunction
Retinitis Pigmentosa
Autosomal Recessive
Decreased night vision (loss of rod cells) and later cones, and peripheral vision
Bony spicules looking dark and blemish specks with soft edges form around the retina
ABC Tr dysfunction
Build up of all-trans- retinals, photoreceptor cells health degenerates
MACULA DEGENERATION
11-cis -retinal + Opsin on disc membrane
Covalently bind in a Schiff base = Functional Rhodopsin
Retinitis Pigmentosa
What Causes this
Oxidative or inflammatory changes in the RPE and retina from envr. or genetic reasons
- Retinoid cycle maintains vision with LRAT and RPE65
- High photon light exposure can increase toxic retinal metabolites formed
- >accumulation of metabolites through life causes photoreceptor degeneration
Macula Degeneration AMD (Macula is in the retinal next to the fovea=where light is focused)
What it looks like
What happens
What causes this
Atrophy, hemorrhage, Drusen spots seen more posterior part by fovea
Loss of central field vision
Aging over 70yo
Smoking for over 20years
Diet is low in antioxidants and Zn, Omega-3, and high in fat)
Obesity= metabolites can bind with cholesterol
Csucasian
ABCA4 transporter mutation = Severe central vision loss
= leading blindness in over 50yo
