Cataract.

Cataract

1. Cataract

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 o f 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 14 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. C auses and risk factors: S moking Obesity Eye injuries UV Malnutrition Family history . Metabolic problems, such as diabetes . Aging (most common). cataracts 16

17. Genetics of cataract: M ost 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. 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. 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: Those linked to the genes coding for connexin proteins Those linked to the crystallins of the lens Those linked to currently unidentified genes

24. Connexins: T ransmembrane 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 . C onnexin 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. C rystallins: L ong-lived proteins located inside lens fibers, maintenance of transparency and refractive power . Approximately 90 % of the lens proteins are crystallins. T hree 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 : Glycolysis The Pentose Phosphate Shunt, and 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 = 100 μ M Glucose Polyol Pathway Sorbitol Accumulation of sorbitol in lens Hyper osmotic effect- Polyol pathway: Cataracts 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/ medlineplus nlm.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.

35. 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 β B3-Crystallin Autosomal Recessive Cataract  Prevalence of Cataract In Pakistan: Genetics of cataract Richard A. Armstrong BSc, Dphil Cataract Special 2005.

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

37. References: Suddarth and Bruner text book Medical Surgical Nursing (Edi: 12 th , 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_Pakistan_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.

38. Thanks!