OPA3: a novel gene and mechanism in cataractogenesis

白内障是由于眼睛晶状体中的混浊造成的，到目前为止，还没有已知的方法来防止这种额叶随着年龄的增长而发生。白内障是导致人类视力丧失的最常见原因，全世界至少有2500万人失明，1.1亿人视力受损。尽管做了手术，但全世界的盲人人数每年都在稳步增加。成人白内障已被证明具有环境和遗传成分，有20多个白内障基因座和10个遗传性白内障基因。最近，一种名为OPA3的新基因的两个杂合错义突变被报道在白内障(特别是蓝点型)和视神经萎缩的患者中。OPA3蛋白的功能尚不清楚，但它似乎是针对线粒体的，线粒体是一种微小的亚细胞细胞器。根据我们对眼睛晶状体发育机制的了解，OPA3基因很有可能在白内障形成的研究中被证明是有兴趣的。程序性细胞死亡(细胞凋亡)的机制与未成熟的晶状体纤维细胞失去细胞器和细胞核并变得透明的过程被认为是相关的。有证据表明，OPA3可能具有抗细胞凋亡的作用，因此它被认为是第一个通过这一机制导致白内障发生的基因。我们计划对蓝点白内障家族和个体进行OPA3突变筛查。我们还计划探索OPA3在眼睛和晶状体发育中和成年组织中的表达。最后，我们将使用细胞系和小鼠模型来探索OPA3的功能。

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.