Functional Analysis of Novel Genes in Eye Development and Vision

1：血小板衍生生长因子D（PDGFD）属于PDGF/VEGF家族。PDGFD在控制透镜生长中具有关键作用，并且抗PDGFD强烈抑制透镜上皮细胞增殖。这一发现表明PDGFD在眼组织协调生长机制中的主要体内作用。 PDGFD也在光感受器中表达，在突触末端具有显著的定位。PDGFD基因的功能性启动子已被鉴定，并正确指导GFP报告基因在眼组织中的表达。小鼠中PDGFD的条件性敲除接近完成。 2：Lengsin是谷氨酰胺合成酶（GS）超家族的新成员，对脊椎动物眼透镜具有特异性。Lengsin在终末分化的次生纤维细胞层中特异性表达，其中细胞核和其他细胞器丢失，细胞骨架和细胞内连接重组。 Y2 H实验表明，晶状体蛋白作为透镜主要细胞骨架成分的分子伴侣，参与晶状体终末分化过程中细胞成分的重组。 3：补体因子H（CFH）在老年性黄斑变性（AMD）的发生发展中具有重要作用。使用酵母双杂交文库的老年人RPE/脉络膜和视网膜和诱饵结构的AMD相关的结构域7的CFH，我们已经确定了潜在的重要目标CFH结合在人RPE/脉络膜。这些结果已被免疫荧光定位证实，并对AMD进展的干预具有意义。 Retbindin是一种新的视网膜蛋白。我们创造了转基因小鼠来过度表达人retbindin。这些已经使用定制的cDNA微阵列进行了分析。结果表明retbindin可能在感光细胞功能和活性中起作用。

1: Platelet-derived growth factor D (PDGFD) belongs to the PDGF/VEGF family. PDGFD has a key role in control of lens growth and anti-PDGFD strongly inhibits lens epithelial cell proliferation This finding suggests a major in vivo role for PDGFD in the mechanisms of coordinated growth of eye tissues. PDGFD is also expressed in photoreceptors with striking localization in the synaptic ends. A functional promoter of the PDGFD gene has been identified and correctly directs expression of a GFP reporter to eye tissues. A conditional knock out of PDGFD in mouse is nearing completion. 2: Lengsin is a novel member of the glutamine synthetase (GS) superfamily that is specific for the vertebrate eye lens. Lengsin is expressed specifically in the layer of terminally differentiating secondary fiber cells in which nuclei and other organelles are lost and cytoskeleton and intracellular junctions are reorganized. Y2H experiments suggest that lengsin has a role as a chaperone of major cytoskeletal components of the lens and participates in the reorganization of cellular components in terminla differentiation.A knock out model of lengsin is now completed and is being examined. 3: Complement factor H (CFH) has an important role in the development of 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 have implications for intervention in the progression of AMD. 4: Retbindin is a novel protein of the retina. We created transgenic mice to overexpress human retbindin. These have been analyzed using custom cDNA microarrays. Results suggest that retbindin may have a role in photoreceptor function and activity.