Discovering the genetic factors in eye disease

Abstract

Eye disease is an increasing problem, exacerbated by ageing populations in most countries. The National Eye Institute in the USA predicts that the cases of age-related macular degeneration (AMD) and glaucoma around the world will double by 2050. According to the World Health Organisation, these two diseases account for six per cent of all cases of visual impairment and blindness globally. Visual impairment affects quality of life and productivity and is therefore an important area of research. Professor Takeshi Iwata’s laboratory is making ground-breaking discoveries in the specialist area of genetically-influenced retinal diseases. Most eye diseases are partly due to genetics, but the influence of a person’s genotype is more profound in hereditary diseases such as retinitis pigmentosa and macular dystrophy. Specific genotypes are less influential, but play a role in AMD and glaucoma. The Iwata laboratory investigates AMD, glaucoma and 36 hereditary retinal diseases, to determine the genetic mutations that cause or predispose a patient towards developing disease. Iwata says: ‘Our goal is to develop therapies for retinal eye diseases based on fundamental research into their molecular mechanisms.’ Determining the genetic mutations behind each disease is the first step to realising this goal. As many of the hereditary retinal diseases are rare, collaboration is very important to the laboratory’s work. To collect samples from a large number of patients, Iwata explains: ‘We founded the Japan Eye Genetics Consortium (JEGC), a group comprising 30 ophthalmology departments throughout Japan.’ Clinicians enter patients’ phenotype information into a national genotype-phenotype database and send saliva or blood samples to the Iwata laboratory for gene analysis. Iwata explains: ‘Following analysis, we upload whole exome and genome analysis results to the database to share amongst the collaborators.’ The JEGC is already yielding important results. 80 per cent of families studied were found to have previously unidentified mutations. Functional analysis is underway to characterise each of these gene mutations in detail. Over 1366 family pedigrees have been collected, and the consortium aims to gather 5000 in total. In 2014, a more ambitious consortium was launched. The aim of the Asian Eye Genetics Consortium (AEGC), Iwata explains, is: ‘to identify all the gene mutations responsible for hereditary eye diseases in the Asian population.’ Over 150 scientists from 20 countries have been brought together through the consortium.