LENS & CATARACT Prof. Naimatullah Khan Kundi Head, Department of Ophthalmology Khyber Teaching Hospital Peshawar
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LENS & CATARACT
Prof. Naimatullah Khan Kundi
Head, Department of Ophthalmology
Khyber Teaching Hospital
Peshawar
Lens & Cataract (Biochemistry)
Molecular Biology
Lens proteins conc. 33% structural proteins
Fibers Proteins:
1. Crystallins - Water soluble group 86% (a, b, r)
2. Water insoluble fraction
Lens & Cataract (Biochemistry)
Molecular Biology
Crystallins: Intracellular (within the plasma membrane of the
lens epithelium and fiber cells)
Water insoluble fraction associated with fiber plasma
membranes
Brown cataract (Brunescent) – Amount of insoluble proteins correlate with
degree of opacification (90% of nuclear proteins insoluble)
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism
Glucose – (hexokinase) G6P – Enters
Anaerobic Glycolysis
Pentose Phosphate Pathway / HMP shunt
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism
Anaerobic Glycolysis:
More active
Provides most of the high energy phosphate bonds for
lens metabolism
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism
HMP Shunt / Pentose phosphate pathway:
Less active pathway of G6P utilization in the lens
5% of lens glucose metabolized by this route
This pathway stimulated in the presence of high levels of
glucose
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism (Cont’d)
Sorbital pathway
Aldose reductase has a key role in the development of
sugar cataract
Normally < 4 % of lens glucose converted to sorbital
When glucose increased in the lens, sorbital pathway
activated relatively more than glycolysis and sorbital
accumulates
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism (Cont’d)
Sorbital pathway (Cont’d)
Sorbital – s. dehydrogenese fructose:
(This enzyme has low afinity, hence sorbital
accumulates + poor permeability of the lens to
sorbital)
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism (Cont’d)
Sorbital pathway (Cont’d)
Sorbital + Fructose:
Increased Osmotic pressure within the lens, drawing
in water
Energy dependent pumps of the lens are
overwhlemed
Result: Lens fibers swelling disruption of the
normal cytoskeletal architecture lens opacification
Lens & Cataract (Biochemistry)
Carbohydrate Metabolism (Cont’d)
Galactose
Galactose 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
Mechanisms
Free radicles generated as a result of:
Normal metabolic activities
External agents (Radiant energy)
Lens & Cataract (Biochemistry)
Oxidative Damage and Protective
Mechanisms
These highly free radicles damage the lens fibers
Oxygen 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
Mechanisms
Protective lens enzymes against free radicles /
oxygen damage:
Glutathione peroxidase
Catalase
Superoxide Dimutase
Vit. E & C present in the lens also protect against
damage (free radicle scavengers)
