The document discusses the biochemistry of the lens and cataracts. It explains that the lens contains high concentrations of structural proteins called crystallins that make up 86% of lens proteins. The document also describes carbohydrate metabolism pathways in the lens, including anaerobic glycolysis and the pentose phosphate pathway. It further discusses how accumulation of sorbitol through the aldose reductase pathway can disrupt lens fiber architecture and lead to cataract formation. The document also mentions protective mechanisms in the lens against oxidative damage from free radicals.

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)