Cataracts

Presented By-

Bhupender Verma

M.Sc. (F) MHG,BHU

Clinical Genetics presentation

on

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 abnormalities

Lowe syndrome

neurofibromatosis 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/Cataract

8. http://eyeinstitutenc.com/cataract/

Thank you