OPA3: a novel gene and mechanism in cataractogenesis

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Cataract is due to cloudiness in the lens of the eye and so far, to date, there is no known way to prevent this fronm happening with age. Cataract is the most common cause of visual loss in humans, with at least 25 million blind and 110 million visually impaired world-wide. Despite surgery the number of patients who are blind world-wide increases steadily year on year. Adult cataract has been shown to have an environmental and a genetic component and there are over 20 cataract loci 10 genes for inherited cataracts. Recently, two heterozygous missense mutations in a new gene called OPA3 have been reported in patients with cataract (particularly the blue-dot type) and optic atrophy. The function of the OPA3 protein is not known, but it appears that it is targeted to mitochondria, which are tiny sub-cellular organelles. From what we know of the mechanism of development of the lens of the eye it appears highly likely that the OPA3 gene will prove interesting in the study of cataract formation. The mechanisms of programmed cell death (apoptosis) and the processes by which immature lens fibre cells lose their organelles and nuclei and become transparent are thought to be related. There is some evidence that OPA3 may act in an anti-apoptotic role and therefore it is postulated to be the first gene to cause cataractogenesis by this mechanism. We plan to screen blue-dot cataract families and individuals for mutation in OPA3. We also plan to explore the expression of OPA3 in the eye and lens in developing and adult tissue. Lastly, we shall explore the function of OPA3 using cell lines and a mouse model.