Cataracts

Presented By-Bhupender Verma

M.Sc. (F) MHG,BHU

Clinical Genetics presentation

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Overview Introduction to vertebrate eye lens

Embryonic development of lens

Cataracts introduction

Types & Clinical features of cataracts

Genetics behind cataracts

Population statistics

Prognosis & treatment

Lens Introduction• Biconvex transparent

structure• Focuses light on retina• Ectodermal origin• Lens structure and

function: Lens capsule Lens epithelium Lens fibers Accommodation:

changing the power of the lens

Crystallin proteins and transparency

capsule

Lens Primary nucleus

Equator

Lens cortex

Epithelium

Fiber cell

• 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 process cells migrate toward center from lens cortex and outer layers.

Genetics of embryonic development of lens

• Interactions of neural tube & epidermal thickenings called Placode e.g. Olfactory, otic or lens placodes.

Genetics in Development

Pax6ShhPax2

BMPs

RxOtx2Six3

Sox2

MITF

Genetics in Development

Pax6

Sox2

L-maf Continual expression of Crystallin

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

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

• Polar cataract

• Pulverulent cataract

• Cerulean cataract

• Lamellar cataract

• Nuclear cataract

• Cortical cataract

• Sutural cataract

• Aculeiform cataract

• Total cataract

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

• 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

• 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 abnormalitiesLowe syndromeneurofibromatosis type 2

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

• 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

Genes involved in inherited cataracts

Epidemiology

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

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

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, replaced with IOL

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

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.

References:1. Congenital Cataracts and their Molecular Genetics-J.

Fielding Hejtmancik; Semin Cell Dev Biol. 2008 April; 19(2): 134–149

2. 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 : 489-494

3. Human molecular genetics: mechanism of inherited diseases- J J Pasternak; 2nd edition, 2005

4. Death and DALY estimates for 2004 by cause for WHO Member States;World Health Organization. who.int. 2004

5. Developmental Biology- Scott F. Gilbert ; 8th edition, 2006

6. http://www.nei.nih.gov/health/cataract/cataract_facts.asp

7. http://en.wikipedia.org/wiki/Cataract8. http://eyeinstitutenc.com/cataract/

Thank you