EYE METABOLISM AND VISION

Cornea
 Must be crystalline = avascular
 Energy source:Glucose – major metabolic fuel = 30% glycolysis, 65% HMP, Highest PPP activity
 Corneal epithelium – permeable to atmospheric O2  formation of various active oxygen species
o Ex: Sulfhydryl groups oxidized to disulfides
o Reduced glutathione reduces oxidized compounds to native states; regenerated by GSH reductase using NADPH
 Protective mechanisms
o GSH reductase, G6PDH – against disulfides and oxygen species
o aldehyde dehydrogenase (ADLH3A1) – against harmful aldehydes

Lens
 Divides eye into anterior chamber (with aqueous humor) and posterior chamber (with vitreous body)
 No blood supply yet metabolically active  aqueous humor for nutrition and waste elimination
 Grows peripherally towards center, core contains cells since birth  aging = ↑ weight and thickness, ↓ elasticity = presbyopia
 Made up of water and proteins (α, β & γ crystallins, albuminoids, enzymes, membrane proteins) all in crystalline state
 CHONs maintained in native unaggregated state against insults via:
o Na-K ATPase - osmolarity
o GSH reductase – redox state, UV irradiation
o new CHON synthesis for growth and maintenance – replacement of metabolites

 Energy source: glucose = 85% anaerobic glycolysis + 10% HMP + 3% TCA

 Cataract – loss of osmolarity and changes in lens protein solubility  regions of high light scatter; Tx: lens replacement
o Senile – due to aging, CHON breakdown (starts at C terminal, deamidation and racemization of aspartyl residues)
o Diabetic - ↑ lens osmolarity due to stimulation of polyol pathway

 ↑ sorbitol = inability of sorbitol to rapidly diffuse out, not used for energy, increased Ald Red and Polyol DH enzyme activities
• Aldose reductase = glucose  sorbitol; ↑ Km = triggers with high glucose levels, diverts glycolysis to polyol pathway
• Polyol DH = sorbitol to fructose, allows regeneration of glucose
 ↑ sorbitol = ↑ lens osmolarity (attracts water), alters structural organization of crystalline CHONS, ↑ CHON aggregation & denaturation

Retina
 Relies heavily on anaerobic glycolysis, but is very vascular
 Fovea centralis – devoid of blood vessels
 Mitochondria in rods and cones, absent in outer segments (pigment layer)
 Lactate DH uses either NADH + H+ or NADPH, active due to anaerobic EMP

Vision
 Photochemical, biochemical and electrical events
 Rods and cones –flattened disks that contain rhodopsin (photoreceptor pigment, rods) and red, blue and green pigments (cones)
 Contain 2 types of ion channel proteins
o Na-Ca channel = closes with ↓ cGMP
o Na-Ca/K exchanger = always open, maintains negative charge
 Rhodopsin – transmembrane protein, opsin + 11-cis retinal, 40kDa, 7 transmembrane helices
 11-cis retinal – attached to protonated Schiff base to ε-amino of lysine 296 of 7th helix, derived from β carotene / VitA / retinal esters
o Cis (visual purple) + light  trans (bleached, visual yellow)

Formation of Rhodopsin, Events in Vision and Regulation

Process / Event Substrate Product Notes
β carotene All-trans retinol Dioxygenase  reductase
All-trans retinol All-trans retinal
Formation
All-trans retinal 11-cis retinal Isomerization
11-cis retinal + opsin Rhodopsin Protonated Schiff base to ε-amino of Lys 296 @ 7th helix
Metarhodopsin II
Rhodopsin + photon Goes through several intermediates
(activated rhodopsin)
Metarhodopsin II All-trans retinal + opsin Dissociation of rhodopsin
Photochemical
All-trans retinal All trans retinol
All trans retinol 11-cis retinol
11-cis retinol 11-cis retinol Oxidation, regeneration, uses IRBP (interphotoreceptor binding protein)

Metarhodopsin II activates transducin
Biochemical Active transducin activates phosphodiesterase (PDE)
PDE hydrolyzes cGMP to 5’GMP
↓ GMP  NaCa channels close
Electrical Hyperpolarization generates electrical impulse
Activated rhodopsin + rhodopsin kinase  Arrestin
Regulation Transducin α subunit has GTPase
↓ Ca activates GC = GTP  cGMP
Trimeric (α, β, γ) G-protein, inactive form = α subunit + GDP 
activation = α + GTP, 500 transducin activated per activated rhodopsin
Heterotetrameric (αβγ2 in rods; α2γ2 in cones) protein 
activation = dissociation of 2γ (regulatory subunit), 500 PDE activated
Causes ↓ cGMP levels in cell, 105 cGMP hydrolyzed
250 Na channels close, Na cannot enter cell
1 mV hyperpolarization, generates nerve impulse
Diverts regenerative pathway of rhodopsin
Can inactivate itself
Opens Na-Ca channel

Rods and Cones

Cell Pigment Color Wavelength Condition Chromosome Notes
Rods Rhodopsin 3 For dark vision
Cyanopsin Blue 420 nm Tritanopia 7 For color vision, trichromatic, discrimination via visual
Cones Iodopsin Green 535 nm Deuteranopia X pigment protein + 11-cis retinal double bond system =
Porphyropsin Red 565 nm Protanopia X energy level and absorption spectra