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1. LENS & CATARACT
Prof. Naimatullah Khan Kundi
Head, Department of Ophthalmology
Khyber Teaching Hospital
Peshawar

2. 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

3. 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)

4. Lens & Cataract (Biochemistry)
 Carbohydrate Metabolism
 Glucose – (hexokinase)  G6P – Enters
 Anaerobic Glycolysis
 Pentose Phosphate Pathway / HMP shunt

5. Lens & Cataract (Biochemistry)
 Carbohydrate Metabolism
 Anaerobic Glycolysis:
 More active
 Provides most of the high energy phosphate bonds for
lens metabolism

6. 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

7. 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

8. 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)

9. 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

10. 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

11. Lens & Cataract (Biochemistry)
 Oxidative Damage and Protective
Mechanisms
 Free radicles generated as a result of:
 Normal metabolic activities
 External agents (Radiant energy)

12. 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

13. 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)