ophthalmologicical biochemistry

LENS & CATARACT

Prof. Naimatullah Khan KundiHead, 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


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)


Carbohydrate Metabolism

Glucose – (hexokinase) G6P – Enters

Anaerobic Glycolysis

Pentose Phosphate Pathway / HMP shunt



Anaerobic Glycolysis:

More active

Provides most of the high energy phosphate bonds for

lens 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


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



Sorbital pathway (Cont’d)

Sorbital – s. dehydrogenese fructose:

(This enzyme has low afinity, hence sorbital

accumulates + poor permeability of the lens to

sorbital)



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



Galactose

Galactose is also substrate for aldose reductase

producing galactital (Dulcitol)

Galactose is not substrate for alcohol dehydrogenese

and thus rapidly accumulates


Oxidative Damage and Protective Mechanisms

Free radicles generated as a result of:

Normal metabolic activities

External agents (Radiant energy)



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



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)

ophthalmologicical biochemistry

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