Mitochondrial shaping proteins in models of optic neuropathy

遗传性视神经疾病是发达国家儿童失明的最常见原因之一。遗传性视神经疾病不仅很常见，而且目前也完全无法治疗和治愈。本工作的目的是在了解线粒体融合/分裂通路和线粒体成形基因的表达、调控和调控的基础上，阐明预防视神经病变的策略。有越来越多的已知基因参与控制细胞中线粒体的形状，从而控制线粒体的功能。其中一些已经被证实与遗传性视神经病变有关。在短期内，需要发现新的基因，以便进行诊断筛查、临床和分子诊断和治疗、评估基因/表型相关性和预后咨询，从而改善对今天的S患者这些疾病的全球管理。这项研究的具体成果将是拓宽遗传性视神经病变的遗传谱，并阐明这些基因在神经组织中的表达和功能。这项研究还将专注于通过减少或移除这些基因中选定的基因在视网膜中的表达来建立真正的动物疾病模型，并研究这对线粒体成形以及视网膜和视神经的组织和形态的影响。这将使我们能够理解这些基因通过对视网膜神经节细胞的假定作用而在导致失明方面发挥的具体作用。只有通过扩大我们对这组重要生理基因的理解，我们才能理解为什么这一微妙机制中的异常可能会特别导致失明。

Inherited optic neuropathies are amongst the most common causes of childhood blindness in the developed world. Not only are inherited optic neuropathies common but they are also currently completely untreatable and incurable. The purpose of this work is to cast light on strategies for preventing optic neuropathy based on understanding the expression, regulation and modulation of mitochondrial fusion/ fission pathways and mitochondrial shaping genes. There are an increasing number of genes known to be involved in controlling the shape, and hence the function of, mitochondria in the cell. Some have all ready been identified as being involved in causing inherited optic neuropathy. In the short term, new genes need to be discovered to permit diagnostic screening, clinical and molecular diagnosis and management, assessment of genotype/ phenotype correlation and prognostic counselling, and hence improve the global management of these conditions for today?s patients. Concrete outcomes of this research will be to broaden the genetic spectrum of inherited optic neuropathy and cast light on the expression and function of such genes in neural tissue. The research will also focus on developing real animal models of disease by reducing or removing the expression of selected of these genes in the retina and studying the effect this has on mitochondrial shaping and retinal and optic nerve histology and morphology. This will enable an understanding of what role these genes have specifically in causing blindness by their putative effects on retinal ganglion cells. Only by broadening our understanding of this group of physiological vital genes will we be able to understand why abnormalities in this delicate mechanism may lead specifically to blindness.