2. BIOCHEMISTRY OF THE LENS
• MAIN CONTENTS ARE
WATER (65%)
PROTEINS(34%)
LIPIDS,CHO AND TRACE ELEMENTS(1%)
3. 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
5. WATER SOLUBLE PROTIENS
• alpha crystallins-more
• beta gamma crystallins-less
they bind to partially denatured protiens in lens
and prevent aggregation
6. 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
7. LENS METABOLISM
• Continous supply of ATP required for-
1. Transport of ions and aminoacids
2. Maintanence of lens dehydration
3. Continous protein synthesis
4. GSH synthesis
• Major site – epithelium
• Source of nutrient supply-aqueous
humour
8. 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
9.
10. 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
11. 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
12. 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
13. OXIDATIVE DAMAGE AND PROTECTIVE
MECHANISMS
• FREE RADICALS-SCAVENGED BY GLUTATHIONE
• VITAMIN E AND ASCORBIC ACID IN LENS ALSO ACT AS
FREE RADICAL SCAVENGERS
14. • EXPOSURE TO LONG TERM HYPERBARIC
OXYGENOPACIFICATION OF LENS
15. 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
16. • 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 here
PASSIVE-water,ions and waste products of metabolism
18. 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
19. 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
20. CATARCTOGENESIS
INCREASED 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
21. 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.,
22. AGE RELATED CATARACTS
• Most commomest
• B/L and asymmetrical
• Three main types
1.Nuclear cataracts
2.Cortical cataracts
3.Posterior subcapsular cataracts
23. 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
24. • 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
25.
26. 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
vision
Risk factors
• Exposure to sunlight
• Thinner lens
• DM
27. 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
28.
29. 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
30.
31. 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
32.
33. SUGAR CATARACT
• galactosemic cataract
• true diabetic cataract-aldose reductase
• HOWEVER IN HUMANS
1.SORBITAL LEVELS NEVER HIGH
2.ALDOSE REDUCTASE VERY LESS
3.ANY SORBITAL QUICKLY METABOLISED TO FRUCTOSE
RECENT HYPOTESIS SHOWS AGES(ADVACED GLYCATION END
PRODUCTS) PLAY MAJOR ROLE
34.
35. 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
36. 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 formed
INFRARED RAYS
Coz post sub capsular opacities
Seen in glass workers
Glass bowlers cataract
37. 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
38. 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