Cataract

Cataract

Contents:Anatomy of EyeIntroduction of cataractClassifiactionPathophysiologyGenetics involved Biochemical pathwaysTest and treatmentPrevalence of cataractReferences

IRIScolored part of eye surrounding pupil. to control size of pupil through contraction or expansion of muscles of iris. PupilAnatomy of Eye:

SCLERA

Cornea Lens

Retina Anatomy of Eye:

Macula

CATARACTA(LATIN) = MEANING WATERFALLCataract:

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.

Normal eyeInfected eye

Cataract Vs. normal eye:

Cataract Symptoms:

blurred vision due to scattering of light on the retina

Cataract Symptoms:

glared viewi.e.(trouble driving at night)

Cataract Symptoms:

change in color visiondimness

age of onset

CONGENITAL

senile SUB CAPSULAR CATARACT

CAPSULAR CATARACT

morphology

IMMATURE CATARCTMATURE CATARACT maturity

Cataract Cataract classification:

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

PATHOPHYSIOLOGY:1.Nuclear:

Central opacity in lensAssociated with myopiaWorsen on progressionGenetic cause = 48%Environmental cause = 14%

2.Cortical:

Involve the interior and posterior equatorial cortexof the lensWorst in very bright lightGenetic cause = 37-58 %Environmental cause= 11-37%

cataracts 14PATHOPHYSIOLOGY:

3.Posterior sub capsular :

occurs in front of posterior capsuleMostly occurs in youngersAssociated with prolongeduse of corticosteroids, diabetes, ocular traumaNear vision is diminished

PATHOPHYSIOLOGY:

Causes and risk factors:Smoking ObesityEye injuriesUV MalnutritionFamily history.Metabolic problems, such as diabetes.Aging (most common).

cataracts 16

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.

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.

Autosomal dominant inheritance:

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.

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 traitsMales are never carriersA single dose of mutant allele in a male will produce a mutant phenotype regardless of whether it is dominant or recessive

X linked dominant

X linked recessive3. X-linked inheritance:

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 proteinsThose linked to the crystallins of the lensThose linked to currently unidentified genes

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

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 , , presence of cataract is associated with gene locations at sites involving the crystallin genes.

Crystallins:Locus 2q33-35 is the site of the -crystallin cluster of genes (A, B, C, D, E, F, G). Of this cluster, mutations in D and E have been associated with progressive nuclear cataract and pulverulent cataract respectively.

mutation of the B2 gene on 22q is associated with progressive nuclear cataract and mutations within the -crystallin cluster on 17q with nuclear cataract.

HSF4, which regulates transcription of heat-shock proteins, including lens B-crystallin.

HSF4 mutations are associated with both autosomal-dominant and recessive cataracts.

LocusInheritanceCandidate GenesCataract Type1q22-30ADConnexin 50Pulverulent2q33-35AD-crystallin clusterPulverulent, nuclear13q11-12ADConnexin 46Nuclear pulverulent17qAD-crystallin clusterLamellar, zonular nuclear22qAD-crystallin clusterCaerulean, pulverulent6p24AR?CongenitalXp22.3-21.1X?Congenital

Gene locations and candidate genes linked to various types of cataractGenetics of cataract Richard A. Armstrong BSc, DphilCataract Special 2005.

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

AgingDecrease in Hexokinase ConcentrationPoor control of electrolyte balanceDrop in ATP levelMassive influx of water into the lensDisorganization of structured proteins in the lensAggregation and precipitation of proteinsGlycolysis pathway:Cataracts

Metabolization of 14% glucoseNADPH + H+ synthesis by glucose-6-phosphatePentose phosphate shunt pathway:

Saturation of Hexokinase at high glucose level in blood(Km = 100MGlucosePolyol PathwaySorbitolAccumulation of sorbitol in lensHyper osmotic effect-Polyol pathway:Cataracts

Influx of excess water through aquaporin channels(Aldose Reductase)

(Polyol dehydrogenase has low Km for sorbitol)

Polyol pathway:

Tests and diagnosis for cataract:Visual acuity test:Slit lamp examinationRetinal examination

nlm.nih.gov/medlineplus

nlm.nih.gov/medlineplus

Home remedies:

Use magnifying glass to readUse better lampsWear sunglasses/broad-brimmed hat to reduce glareLimit your night driving

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 lensPositioned in same place of natural lens and it becomes a permanent part of eye.

Chromosome/Genes/LociCataract TypeChromosome 19q13 Autosomal Recessive Congenital Nuclear CataractsExon 11 ofHSF4 Autosomal Recessive CataractChromosome 7q21.11-q31.1 Autosomal Recessive Congenital CataractFYCO1Autosomal Recessive cataractEPHA2Autosomal Recessive Congenital CataractsLCA5 CataractsChromosome 2p12 Autosomal Dominant Nuclear CataractB3-Crystallin Autosomal Recessive Cataract

Prevalence of Cataract In Pakistan:Genetics of cataract Richard A. Armstrong BSc, DphilCataract Special 2005.

http://mmhpk.org/publications.htmlBreakdown of Cataract In Pakistan:

References: Suddarth and Bruner text book Medical Surgical Nursing (Edi: 12th, 2010) published by Wolter Kluwer health 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;35:7177.

Kaul H, Riazuddin SA, Yasmeen A, et al. A new locus for autosomal recessive congenital cataract identified in a Pakistani family. Mol Vis.2010;16:240245.

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;79:358364.

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