PHYSIOLOGY OF LENS AND CATARACTOGENESIS

BIOCHEMISTRY OF THE LENS• MAIN CONTENTS ARE WATER (65%) PROTEINS(34%) LIPIDS,CHO AND TRACE ELEMENTS(1%)

WATER

• relatively dehydrated organ• cortex more hydrated than nucleus• 80% is free and 20% is bound• low water is natural consequence of need for

maintining refractive index• no significant alteration in hydration with age

PROTEINS

• conc of proteins in lens is higher than any organ in the body

WATER SOLUBLE PROTIENS

• alpha crystallins-more• beta gamma crystallins-less

they bind to partially denatured protiens in lens and prevent aggregation

WATER INSOLUBLE PROTIENS

• UREA SOLUBLE .CYTOSKELETAL PROTEINS .VIMENTIN AND BEADED FILAMENTS .GENETIC DISRUPTION OF BEADED FILAMENTS L/T CATARACT FORMATION

• UREA INSOLUBLE .MEMBRANE INHIBITORY PROTEINS .MEMBRANE PROTEINS .SERVES TO REDUCE LIGHT SCATTERING BETWEEN CELLS

LENS METABOLISM

• Continous supply of ATP required for-1. Transport of ions and aminoacids2. Maintanence of lens dehydration3. Continous protein synthesis4. GSH synthesis

• Major site – epithelium• Source of nutrient supply-aqueous humour

GLUCOSE METABOLISM

• Energy production entirely dependent on glucose metabolism

• Glucose enters lens by simple diffusion and facilitated diffusion

• Epithelial cells- GLUT-1• Lens fibre cells-GLUT-3• Glucose is rapidly metabolized via glycolysis so

that level of free glucose in lens < 1/10 level in aqueous

1)Anaerobic metabolism• Accounts for 85% of glucose metabolism by lens• Provides > 70% of energy for lens• 1 mole of glucose gives 2 moles of ATP• Lactate generated undergoes 2 pathways of metabolism• Further metabolism via Kreb’s cycle• Diffusion from lens into aqueous

2)Aerobic metabolism (Krebs cycle)• Limited to epithelium• 1 mole of glucose gives 38 moles of ATP• Only 3% of lens glucose metabolized by this pathway• But generates up to 20% of total ATP needs of lens

3)Hexose monophosphate shunt• Accounts for 5% of glucose metabolism by lens• Important source of NADPH required for other

metabolic pathways e.g. sorbitol pathway and glutathione reductase

4)Sorbitol pathway• Accounts for 5% of glucose metabolism by lens• When sorbitol accumulates within cells of lens, it

sets up an osmotic gradient that induces influx of water and lens swelling, and ultimate loss of lens transparency

WITH AGE

• lens proteins proteolyse dissembly of fibres aggregation of water insoluble proteins scatter light opacification of lens

• glutathione is essential for maintaining a reduced environment any depletion cause cataract

OXIDATIVE DAMAGE AND PROTECTIVE MECHANISMS

• FREE RADICALS-SCAVENGED BY GLUTATHIONE

• VITAMIN E AND ASCORBIC ACID IN LENS ALSO ACT AS FREE RADICAL SCAVENGERS

• EXPOSURE TO LONG TERM HYPERBARIC OXYGENOPACIFICATION OF LENS

PHYSIOLOGY OF LENS• lens cells with highest metabolic rate are at

equator and lens epithelium• cells are connected to each other by gap

junctions and membrane integrated prOtiens

• MAINTANENCE OF LENS WATER AND CATION BALANCE

MOST IMPORTANT MECH FOR MAINTAINING LENS TRANSPARENCY

MAINLY BY ACTIVE AND PASSIVE TRANSPORT MECHANISMS

ACTIVE- AA’S,K,Na,INOSITOL ETC. 90% of energy in the form of ATP utilised herePASSIVE-water,ions and waste products of metabolism

WATER AND ELECTROLYTE TRANSPORTpump leak mechanism

TRANSPORT OF AA

• Also included in pump leak concept• Three types of pumps• Inside the lens aa are utilised for protein

formtion and energy production or diffuse back in to aqueous by leak

FACTORS MAINTAINING TRANSPARENCY

• Thin epithelium• Regular arrangement of lens fibers• Little cellular organelles• Little extracellular space• Orderly arrangement of lens proteins• Relative dehydration• Semipermeable character of lens capsule• Avascularity• Antioxidants

CATARCTOGENESISINCREASED AGE LEADS TO INCREASE WEIGHT AND THICKNESS OF LENS

LENS UNDERGO COPRESSION AND HARDENING(NUCLEAR SCLEROSIS)

AGGREGATION OF PROTIENS ALSO CAUSES FLUCTUATIONS IN RI OF LENS,LIGHT SCATTERING AND DECREASED TRANSPARENCY

CHEMICAL MODIFICATIONS ALSO INCREASES PIGMENTATION GIVING RED YELLOW COLOURS TO LENS

DEC K,GLUTATHIONE AND INC Ca AND Na

RISK FACTORS

• Age >50• Low SES• Sex females>males.however estrogen is

protective• Smoking and alcoholism• Exposure to steroids and radiations• Myopia,DM,HTN,renal failure etc.,

AGE RELATED CATARACTS

• Most commomest• B/L and asymmetrical• Three main types1.Nuclear cataracts2.Cortical cataracts3.Posterior subcapsular cataracts

NUCLEAR CATARACT

• M.C type, >60%• In asian population cortical cat predominates• Nuclear cataract is associated with the oxidative

damage to the proteins and lipids, leading to hardening of the lens nucleus and increased light scattering

• Hardening inc ref powermyopic shiftsecond sight

• The lens normally exists in an extremely hypoxic environment. Patients treated with long-term hyperbaric oxygen therapy develop a myopic shift and,eventually, nuclear cataracts ?why not cortical?

• Post virectomy and age related degeneration of vitreous also plays significan role in nuclear cataracts

CORTICAL CATARACT

• First appear at age of onset of presbyopia• Mature fibres on surface of cells are affected• M.C site is inferonasal quadrant• Starts at periphery and takes years to obscure

visionRisk factors• Exposure to sunlight• Thinner lens• DM

Mechanisms• disruption of pumps• physical or chemical damage to cell plasma proteins • Damage to Ca homeostasis• Glutathione loss

• First sign in SLB is formation of vacuoles and water clefts in anterior and post cortex

• Numerous mech like globular deg and walling off which prevents progression of cataract

PSC

• Caused by cluster of swollen cells at post pole of lens just below capsule

• Opacity in optical axis,disabling

Risk factors• Steroid intake• Exposure to radiation• trauma

SECONDARY CATARACTS

• frequent complication of ecce• ep cells close to equator may diff in to

soemmering’s ring or migrate in to post capsule to form “elschnig’s pearls”

• both scattter light and form sec cataract• cytokine TGF-B plays imp role

SUGAR CATARACT

• galactosemic cataract• true diabetic cataract-aldose reductase• HOWEVER IN HUMANS1.SORBITAL LEVELS NEVER HIGH2.ALDOSE REDUCTASE VERY LESS3.ANY SORBITAL QUICKLY METABOLISED TO FRUCTOSE

RECENT HYPOTESIS SHOWS AGES(ADVACED GLYCATION END PRODUCTS) PLAY MAJOR ROLE

RADIATION CATARACTS• ionizing radiations-xrays or gamma rays

exposure to radiation L/T damage to germinative layers of lens epithelium

COMPENSATORY MITOSIS IN EPITHELIAL CELLS

CELLS DIFF,ELONGATE AND SWOLLEN,CELL VOLUME NOT CHANGED

NUCLEI OF THESE CELLS MOVE POSTERIORLY

BALOON CELS/WELD CELLS FORMED IN P.P L/T PSCO

GLUTATHIONE AND K LEVEL DEC AND Na CONC INC,PROTIEN SYN SLOWS

RADIATION CATARACT

NON IONIZING RADIATIONS-UV RAYS UV-B not UV-A responsible for cortical cataract Mech in humans not clear May be D/T excess formation of free radicals Mainly cortical cataracts are formedINFRARED RAYS Coz post sub capsular opacities Seen in glass workers Glass bowlers cataract

STERIOD INDUCED CATARACT

• Children more susceptible than adults• Mechanism-inc glucose levels inhibition of Na-k-atp pump loss of ATP inc cation pump• Common is PSCO

ELECTRICAL INJURY

• cause protein coagulation and cataract formation

• more likely when the transmission of current involves the patient's head

• Initially,lens vacuoles appear in the anterior midperiphery of the lens, followed by linear opacities in the anterior subcapsular cortex

OTHER CAUSESPHENOTHIAZONES

TRAUMA

SIDEROSIS BULBI

MYOTONIC DYSTROPHY

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