Functional Analysis of Novel Genes in Eye Development and Vision

1：AMD和补体因子H(CFH)。CFH的常见序列变异在决定老年性黄斑变性(AMD)的易感性方面起着重要作用。利用老年人RPE/脉络膜和视网膜的酵母双杂交文库和CFH的AMD相关结构域7的诱饵构建物，我们已经确定了人RPE/脉络膜中潜在的CFH结合的重要靶点。这些结果已被免疫荧光定位和使用天然和重组蛋白结合实验所证实。质谱学正在被用来鉴定与AMD蛋白质沉积形成有关的进一步的复合体成分。这有可能使药物设计干预AMD的进展。AMD应激相关过程的细胞培养模型也在研究中。 2：Retbindin是一种新的视网膜蛋白。我们已经证明了视黄醇结合素本质上是光感受器所特有的，并且人类基因有不同的视锥细胞和视杆细胞启动子。转基因小鼠模型表明，视黄素在控制视网膜中类视黄素和类胡萝卜素水平方面具有作用。一只基因敲除的鼠标已经被创造出来，几乎可以进行评估了 3：鉴定了新的晶状体特异性基因，其特征表明可能在年龄相关性白内障中发挥作用，并建立了两种年龄相关性皮质性白内障的小鼠模型。 4.在小鼠眼部和耳部高表达的miRNA簇被缺失，建立了一种新的听力和视觉障碍模型。

1: AMD and complement factor H (CFH). Common sequence variants of CFH have major roles in determining susceptibility to age-related macular degeneration (AMD). Using yeast 2-hybrid libraries for aged human RPE/choroid and retina and bait constructs for the AMD-related domain 7 of CFH we have identified potentially important targets for CFH binding in human RPE/choroid. These results have been confirmed by immunofluorescence localization and by using native and recombinant protein binding experiments. Mass spectroscopy is being used to identify further components of complexes that are implicated in formation of protein depositions in AMD. This has potential for drug-design to intervene in the progression of AMD. A cell-culture model for stress-related processes in AMD is also being investigated. 2: Retbindin is a novel protein of the retina. We have shown that retbindin is essentially specific for photoreceptors and that the human gene has separate cone and rod cell promoters. A transgenic mouse model shows suggests that retbindin has a role in control of retinoid and carotenoid levels in the retina. A knockout mouse has been created and is nearly ready for evaluation 3: Novel lens-specific genes with characteristics suggesting possible roles in age-related cataract have been identified and two mouse models with age-related cortical cataract have been created. 4: A miRNA cluster with high expression in eye and ear has been deleted in mouse, producing anew model of hearing and vision deficit.