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LENS & CATARACT
Prof. Naimatullah Khan KundiHead, Department of OphthalmologyKhyber Teaching Hospital Peshawar
Lens & Cataract (Biochemistry)Molecular BiologyLens proteins conc. 33% structural proteinsFibers Proteins:Crystallins - Water soluble group 86% (a, b, r)Water insoluble fraction
Lens & Cataract (Biochemistry)Molecular BiologyCrystallins: Intracellular (within the plasma membrane of the lens epithelium and fiber cells)Water insoluble fraction associated with fiber plasma membranesBrown cataract (Brunescent) Amount of insoluble proteins correlate with degree of opacification (90% of nuclear proteins insoluble)
Lens & Cataract (Biochemistry)Carbohydrate MetabolismGlucose (hexokinase) G6P Enters Anaerobic GlycolysisPentose Phosphate Pathway / HMP shunt
Lens & Cataract (Biochemistry)Carbohydrate MetabolismAnaerobic Glycolysis: More active Provides most of the high energy phosphate bonds for lens metabolism
Lens & Cataract (Biochemistry)Carbohydrate MetabolismHMP Shunt / Pentose phosphate pathway:Less active pathway of G6P utilization in the lens5% of lens glucose metabolized by this routeThis pathway stimulated in the presence of high levels of glucose
Lens & Cataract (Biochemistry)Carbohydrate Metabolism (Contd)Sorbital pathwayAldose reductase has a key role in the development of sugar cataractNormally < 4 % of lens glucose converted to sorbitalWhen glucose increased in the lens, sorbital pathway activated relatively more than glycolysis and sorbital accumulates
Lens & Cataract (Biochemistry)Carbohydrate Metabolism (Contd)Sorbital pathway (Contd)Sorbital s. dehydrogenese fructose:(This enzyme has low afinity, hence sorbital accumulates + poor permeability of the lens to sorbital)
Lens & Cataract (Biochemistry)Carbohydrate Metabolism (Contd)Sorbital pathway (Contd)Sorbital + Fructose:Increased Osmotic pressure within the lens, drawing in water Energy dependent pumps of the lens are overwhlemedResult: Lens fibers swelling disruption of the normal cytoskeletal architecture lens opacification
Lens & Cataract (Biochemistry)Carbohydrate Metabolism (Contd)GalactoseGalactose is also substrate for aldose reductase producing galactital (Dulcitol)Galactose is not substrate for alcohol dehydrogenese and thus rapidly accumulates
Lens & Cataract (Biochemistry)Oxidative Damage and Protective MechanismsFree radicles generated as a result of: Normal metabolic activities External agents (Radiant energy)
Lens & Cataract (Biochemistry)Oxidative Damage and Protective MechanismsThese highly free radicles damage the lens fibersOxygen tension in the lens decreases,So free radicles may not involve molecular oxygen Instead the free radicles may react directly with molecules
Lens & Cataract (Biochemistry)Oxidative Damage and Protective MechanismsProtective lens enzymes against free radicles / oxygen damage:Glutathione peroxidaseCatalaseSuperoxide DimutaseVit. E & C present in the lens also protect against damage (free radicle scavengers)