This document provides an overview of cataracts, including their anatomy, classification, pathophysiology, genetics, biochemical pathways, tests and treatments, prevalence, and references. It describes the key structures of the eye involved in cataracts such as the iris, pupil, sclera, cornea, and retina. It classifies cataracts based on location, age of onset, morphology, and maturity. The main pathophysiological mechanisms and risk factors are discussed. Genetic inheritance patterns and candidate genes are outlined. Biochemical pathways like glycolysis, the pentose phosphate shunt, and the polyol route are implicated in cataract formation. Tests, treatments, and prevalence statistics in Pakistan are summarized along with references

2. Contents:
Anatomy of Eye
Introduction of cataract
Classifiaction
Pathophysiology
Genetics involved
Biochemical pathways
Test and treatment
Prevalence of cataract
References

3. IRIS
 colored part of eye surrounding pupil.
 to control size of pupil through
contraction or expansion of muscles of
iris.
Pupil
Anatomy of Eye:

4. SCLERA
Cornea
Lens
Retina
Anatomy of Eye:
Macula

5. ‘CATARACTA’(LATIN) = MEANING ‘WATERFALL’
Cataract:

6. Cataract:
progressive, painless clouding of the natural,
internal lens of the eye.
Opacification and degeneration of lens fibers
The formation of aberrant lens fibers or
deposition of other materials in their place.

7. Normal eye Infected eye
Cataract Vs. normal eye:

8. Cataract Symptoms:
blurred vision
due to scattering of light on the retina

9. Cataract Symptoms:
glared view
i.e.(trouble driving at night)

10. Cataract Symptoms:
change in color vision
dimness

11. age of onset
CONGENITAL
senile
SUB CAPSULAR
CATARACT
CAPSULAR
CATARACT
morphology
IMMATURE
CATARCT
MATURE
CATARACT
maturity
Cataract
Cataract classification:

12. PATHOPHYSIOLOGY:
• Cataracts can develop
in one or both eyes at any
age
• Three most common type
of senile(aged-related)
cataracts are defined by
the location in the lens

13. PATHOPHYSIOLOGY:
1.Nuclear:
 Central opacity in lens
 Associated with myopia
 Worsen on progression
 Genetic cause = 48%
 Environmental cause = 14%

14. 2.Cortical:
 Involve the interior and
 posterior equatorial cortex
of the lens
 Worst in very bright light
 Genetic cause = 37-58 %
 Environmental cause= 11-37%
cataracts
PATHOPHYSIOLOGY:

15. 3.Posterior sub capsular :
 occurs in front of posterior capsule
 Mostly occurs in youngers
 Associated with prolonged
use of corticosteroids, diabetes,
ocular trauma
 Near vision is diminished
PATHOPHYSIOLOGY:

16. Causes and risk factors:
 Smoking
 Obesity
 Eye injuries
 UV
 Malnutrition
 Family history.
 Metabolic problems, such as diabetes.
 Aging (most common).
cataracts

17. Genetics of cataract:
 Most common mode of inheritance is autosomal dominant cataract.
 Autosomal recessive and X-linked forms are also seen
but are uncommon.
 Half of congenital cataract are inherited while age-related cataracts
tend to be multifactorial, with both multiple genes and
environmental factors influencing the phenotype.

18. 1. Autosomal dominant inheritance:
 manifests in the heterozygous state
 In this male and female both are affected.
 Mutation in one allele is enough to express the disease.
 This is vertical transmission.
 The offspring's have 50% chances to have the disease.

19. 1. Autosomal dominant inheritance:

20. 2. Autosomal recessive inheritance:
 only manifest when mutant allele is present in homozygosity.
 Individuals heterozygous for such mutant alleles show no
features of the disorder and are healthy, i.e. they are carriers.

21. 3. X-linked inheritance:
 When a gene for particular disease/trait lies on the X chromosome
it is X-linked
 Males = XY (X from mother, Y from father)
 Females = XX (1 X from mother, 1 X from father)
 X-linked genes are NEVER passed from father to son
 In an affected family affected females must have an affected
father
 Males are hemizygous for x-linked traits
 Males are never carriers
 A single dose of mutant allele in a male will produce a mutant
phenotype regardless of whether it is dominant or recessive

22. X linked dominant X linked recessive
3. X-linked inheritance:

23. Genes & Loci For Cataract:
 currently about 45 genetic loci to which cataracts have been
mapped with specific genes identified is 38,
although the number is constantly increasing.
 The genes linked to cataract will be considered under the following
headings:
a)Those linked to the genes coding for connexin proteins
b)Those linked to the crystallins of the lens
c) Those linked to currently unidentified genes

24. Connexins:
 Transmembrane proteins
 Pulverulent cataract and nuclear Pulverulent cataract are linked to
gene locations at 1q22-30 and 13q11-12 respectively, sites of the
genes that code for the connexin proteins of the lens.
 Connexin 50 (Cx50) and connexin 46 (Cx46), are present in lens fibers
and form the intercellular channels of the lens.
 Cx46 is concerned primarily with lens clarity, and Cx50 with lens
growth.
 Deletion of Cx46 will lead to severe cataract and deletion of Cx50 will
lead to reduce lens growth.
 PAX6 (Paired Box 6) gene and mutation in this gene causes Cataract

25. Crystallins:
 Long-lived proteins located inside lens fibers,
 maintenance of transparency and refractive power.
 Approximately 90% of the lens proteins are crystallins.
 Three basic types of crystallin in the vertebrate lens – α, β, γ
 presence of cataract is associated with gene locations at sites
involving the crystallin genes.

26. Crystallins:
Locus 2q33-35 is the site of the γ-crystallin cluster of genes (γA, γB, γC,
γD, γE, γF, γG). Of this cluster, mutations in γD and γE have been
associated with progressive nuclear cataract and pulverulent cataract
respectively.
mutation of the βB2 gene on 22q is associated with progressive
nuclear cataract and mutations within the α-crystallin cluster on 17q with
nuclear cataract.
 HSF4, which regulates transcription of heat-shock proteins,
including lens αB-crystallin.
 HSF4 mutations are associated with both autosomal-dominant and
recessive cataracts.

27. Locus Inheritance Candidate Genes Cataract Type
1q22-30 AD Connexin 50 Pulverulent
2q33-35 AD γ-crystallin cluster Pulverulent, nuclear
13q11-12 AD Connexin 46 Nuclear pulverulent
17q AD α-crystallin cluster Lamellar, zonular
nuclear
22q AD β-crystallin cluster Caerulean,
pulverulent
6p24 AR ? Congenital
Xp22.3-21.1 X ? Congenital
Gene locations and candidate genes linked to various types
of cataract
Genetics of cataract Richard A. Armstrong BSc, Dphil
Cataract Special 2005.

28. Three metabolic pathways and
one single problem: cataracts
 There are three metabolic pathways which convert glucose in energy
(ATP) and other relevant metabolic molecules. These are:
1. Glycolysis
2. The Pentose Phosphate Shunt, and
3. The Polyol Route

29. Aging Decrease in Hexokinase
Concentration
Poor control of electrolyte
balance
Drop in ATP
level
Massive influx of water into
the lens
Disorganization of structured
proteins in the lens
Aggregation and
precipitation of proteins
Glycolysis pathway:
Cataracts

30. Metabolization of 14%
glucose
NADPH + H+ synthesis by
glucose-6-phosphate
Pentose phosphate shunt pathway:

31. Saturation of Hexokinase at high
glucose level in blood(Km = 100μM
Glucose
Polyol Pathway
Sorbitol
Accumulation of sorbitol in
lens
Hyper osmotic effect-
Polyol pathway:
Influx of excess water
through aquaporin channels
(Aldose Reductase)
(Polyol dehydrogenase has low Km for sorbitol)

32. Polyol pathway:

33. Tests and diagnosis for cataract:
• Visual acuity test:
• Slit lamp examination
• Retinal examination
nlm.nih.gov/medlineplusnlm.nih.gov/medlineplus
Home remedies:
Use magnifying glass to read
Use better lamps
Wear sunglasses/broad-brimmed hat to
reduce glare
Limit your night driving

34. Treatment for cataract:
• Only effective treatment is surgery.
Procedure:
It involves removing the clouded lens
and replacing it with a clear artificial lens.
Artificial lens= intraocular lens
Positioned in same place of natural lens
and it becomes a permanent part of eye.

36. Chromosome/Genes/Loci Cataract Type
Chromosome 19q13 Autosomal Recessive Congenital Nuclear
Cataracts
Exon 11 of HSF4 Autosomal Recessive Cataract
Chromosome 7q21.11-q31.1 Autosomal Recessive Congenital Cataract
FYCO1 Autosomal Recessive cataract
EPHA2 Autosomal Recessive Congenital Cataracts
LCA5 Cataracts
Chromosome 2p12 Autosomal Dominant Nuclear Cataract
βB3-Crystallin Autosomal Recessive Cataract
Prevalence of Cataract In Pakistan:
Genetics of cataract Richard A. Armstrong BSc, Dphil
Cataract Special 2005.

37. http://mmhpk.org/publications.html
Breakdown of Cataract In Pakistan:

38. References:
 Suddarth and Bruner text book Medical Surgical Nursing (Edi: 12th, 2010) published by Wolter Kluwer
health І Lipponcott Williams & wilkins South Asia Advisory Penal
 http://www.world-federation.org/Health/Aeinullah+Eye+Clinics/Mianwali+-
+Pakistan/Articles/115_Patients_screened_39_cataract_surgeries_performed_Aeinullah_Eye_Clinic_P
akistan_month_March_2013.htm
 Dineen B, Bourne RR, Jadoon Z,Shah SP, Khan MA, Foster A, et al, Causes of Blindness and visual
impairment in Pakistan: the Pakistan national blindness and visual impairment survey. Br J
Ophthalmology 2007; 91:1005-10.
 Genetics of cataract Richard A. Armstrong BSc, Dphil Cataract Special 2005.
 Klopp N, Heon E, Billingsley G, et al. Further genetic heterogeneity for autosomal dominant human
sutural cataracts. Ophthalmic Res. 2003;35:71–77.
 Kaul H, Riazuddin SA, Yasmeen A, et al. A new locus for autosomal recessive congenital cataract
identified in a Pakistani family. Mol Vis.2010;16:240–245.
 Valleix S, Niel F, Nedelec B, et al. Homozygous nonsense mutation in the FOXE3 gene as a cause of
congenital primary aphakia in humans.Am J Hum Genet.2006;79:358–364.