Bhupi clinical genetics cataract


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  • After the natural lens has been removed, it often is replaced by an artificial lens, called an intraocular lens (IOL). An IOL is a clear, plastic lens that requires no care and becomes a permanent part of your eye. Light is focused clearly by the IOL onto the retina, improving your vision. You will not feel or see the new lens.
  • Bhupi clinical genetics cataract

    1. 1. Clinical Genetics presentation on Cataracts Presented By- Bhupender Verma M.Sc. (F) MHG,BHU
    2. 2. Overview Introduction to vertebrate eye lens Embryonic development of lens Cataracts introduction Types & Clinical features of cataracts Genetics behind cataracts Population statistics Prognosis & treatment
    3. 3. Lens Introduction• Biconvex transparent structure• Focuses light on retina Equator• Ectodermal origin Lens cortex• Lens structure and function: capsule  Lens capsule  Lens epithelium Lens  Lens fibers Primary  Accommodation: nucleus Epithelium changing the power of the lens  Crystallin proteins and transparency Fiber cell
    4. 4. • Central part of lens • Forms by elongation of posterior epithelial lens vesicle • Contains lens primary nucleus• Anterior epithelium • Cells anterior to central region divide throughout lifetime • Differentiate into fiber cells • Elongates, looses their nuclei & intracellular organelles As part of continuous processcells migrate toward center from lens cortex and outer layers.
    5. 5. Genetics of embryonic development of lens• Interactions of neural tube & epidermal thickenings called Placode e.g. Olfactory, otic or lens placodes.
    6. 6. Genetics in Development MITFBMPs Sox2 Pax2 Shh Pax6 Otx2 Rx Six3
    7. 7. Genetics in Development Sox2 Pax6L-maf Continual expression of Crystallin
    8. 8. What is a cataract?• A cataract is a clouding of the lens in the eye• affects vision• Most commonly associated with breakdown of the lens microarchitecture• Most cataracts are related to aging• Cataracts are very common in older people• Occur in either or both eyes• Cannot spread from one eye to the other• varying in degree from slight to complete opacity• If lens is cloudy from a cataract, the image seen will be blurred• Derives its name due to foggy or misty vision as near waterfall
    9. 9. Classification of Cataracts On etiological basis • Congenital cataracts • Senile cataracts • Secondary cataracts • Traumatic cataracts On the basis of Opacities (capsular/sub capsular) • Polar cataract • Pulverulent cataract • Cerulean cataract • Lamellar cataract • Nuclear cataract • Cortical cataract • Sutural cataract • Aculeiform cataract • Total cataract
    10. 10. • Polar cataract• Pulverulent cataract• Cerulean cataract• Lamellar cataract• Nuclear cataract• Cortical cataract• Sutural cataract• Aculeiform cataract• Total cataract
    11. 11. Causes• Have multiple causes• Often associated with breakdown of the lens microarchitecture• Includes vacuole formation• Disarray of lens cells• Cause large fluctuations in density resulting in light scattering• Accumulation of high molecular weight protein aggregates of approximately 1000 Å or more• Disruption of short-range ordered packing of the lens crystallins
    12. 12. • Disruption of lens microarchitecture and protein denaturation are not mutually exclusive events• mutations in crystallins when sufficient to form aggregates, causes Congenital cataracts• environmental insults such as light, hyperglycemic or oxidative damage contribute to age related cataract• Mutations causing insult to epithelial cell resulting in disturbed homeostasis if, • Severe- congenital cataract • Milder- senile along with environmental factors• Inheritance pattern  Congenital- Mendelian inheritance  Senile- Complex pattern• Exposure to compounds such that H2O2
    13. 13. • In general:  Congenital- infection, developmental defects or mutations  Senile- environmental, UV radiation or smoking or formation of reactive• Cataracts may also be part of multisystem genetic disorders such as:  chromosome abnormalities  Lowe syndrome  neurofibromatosis type 2
    14. 14. Molecular basis• A number of loci have been identified• inheritance pattern of  autosomal dominant  autosomal recessive  X-linked• 14 genes responsible for primary cataract have been identified• 7 of these encode crystallins• Allelic heterogeneity is seen for many Crystallin genes• Crystallin mutations been found to cause  Misfolding & aggregation  Prevent protein-protein interactions that maintain lens transparency  Decrease protein solubility & forms agglomerates• Type of cataract may depend on time of gene expression during lens development
    15. 15. • Connexin 50 & 46 mutations also lead to cataract  Hinder distribution of small molecules to fiber cells  Aberrant gap junctions form  Abnormal fiber cell production & formation• Defective water transport protein  Change in solubility conditions in lens cell  E.g. MIP gene mutation• Disruption of interaction between cytoskeletal proteins  E.g. BSFP2 and alphaA-crystallin• Mutant transcription factors  PITX3, MAF, HSF4
    16. 16. Genes involved in inherited cataracts
    17. 17. Epidemiology
    18. 18. Statistics (Indian)• According to WHO, 47.8% of global blindness is due to cataract in South Asia region• prevalence of blindness in people >50 years of age (presenting vision < 20/200) was observed to be 8.5%• there is a declining trend over the period 1989-2001• 51% of blindness is due to cataract in India• in 2001, there were 7.75 million individuals whose blindness could be attributed to cataract• would increase to 8.25 million by 2020• increase in the total number of cataract blind in the age group above 70 years been observed• From prevalence & CSR statistical data India would be placed in a comfortable position for eliminating cataract blindness by 2020
    19. 19. Diagnosis, Treatment & Prognosis• Visual acuity test: This eye chart test measures how well subject see at various distances.• Dilated eye exam:  Drops are placed in eyes to widen, or dilate, the pupils  special slit lamp used to examine retina and optic nerve for signs of damage and other eye problems• Tonometry: to measure the pressure inside the eye
    20. 20. Treatment• symptoms of early cataract may be improved with new eyeglasses, brighter lighting, anti-glare sunglasses, or magnifying lenses• cataract needs to be removed only when vision loss interferes with everyday activities• Only treatment is surgery• Surgery is of two types-  Phacoemulsification, or phaco  Extracapsular surgery• Natural lens removed, replacedwith IOL
    21. 21. Prognosis• Risk with surgery  Infection & bleeding  Retinal detachment• Cataract removal is one of of the safest and most effective types of surgery• In about 90 percent of cases, people who have cataract surgery have better vision afterward
    22. 22.  Cataract surgical rate (CSR) is a quantifiable measure of the delivery of cataract services in a country. It is thus a good indicator of how well a country is organizing its efforts. A CSR of 3000 was targeted under Vision 2020: the right to sight, for India, by the year 2000.Current trends show that this target has been achieved, but still there are regional disparities across the country. But we are doing good. 
    23. 23. References:1. Congenital Cataracts and their Molecular Genetics-J. Fielding Hejtmancik; Semin Cell Dev Biol. 2008 April; 19(2): 134–1492. Current status of cataract blindness and Vision 2020: The right to sight initiative in India-GVS Murthy et al; indian journal of ophthalmology Year : 2008, Volume:56, Issue:6, Page : 489-4943. Human molecular genetics: mechanism of inherited diseases- J J Pasternak; 2nd edition, 20054. Death and DALY estimates for 2004 by cause for WHO Member States;World Health Organization. 20045. Developmental Biology- Scott F. Gilbert ; 8th edition, 20066.
    24. 24. Thank you