Novel Locus Required For Photoreceptor Survival

描述（由申请人提供）：导致年龄相关性黄斑变性（AMD）和视网膜色素变性（RP）中感光细胞死亡的遗传缺陷是高度异质性的，现在包括超过132个基因的列表。使用果蝇作为解开视网膜变性疾病，如AMD和RP的遗传位点的分子遗传模型，我们最近已经确定了一个全新的一类分子，感光细胞的活力和细胞功能是至关重要的。这是一类钠依赖性协同转运蛋白或协同转运蛋白，其使小分子穿过膜以交换钠。果蝇和人类的光感受器都具有几种转运系统，如钠/钙（-钾）交换体（NCKX）和ABC转运体。基于果蝇和人类视觉系统之间的这些和其他相似之处，我们提出钠依赖性转运蛋白可能是某些遗传遗传形式的人类视网膜变性的关键位点。钠依赖性协同转运蛋白的突变导致果蝇感光细胞病变和年龄相关性视网膜变性。此外，这些突变还导致视紫红质分子量的缺陷。我们提出了钠依赖性协同转运蛋白和视紫红质之间的联系。在许多情况下，钠依赖性共转运蛋白在保护细胞免受氧化损伤方面至关重要。氧化损伤被认为有助于AMD和RP以及糖尿病视网膜病变。因此，钠依赖性转运蛋白可能是某些形式的视网膜变性的重要位点。揭开新型分子的面纱开辟了全新的研究领域，并开发了新的治疗策略。我们的数据继续支持这样的概念：果蝇研究对于揭示人类视网膜变性的基础非常有价值。 果蝇提供了快速洞察新类别的蛋白质，这些蛋白质是感光功能和视网膜疾病的强有力候选者。该应用的高度影响和创新是利用果蝇分子遗传学的力量，为视网膜变性疾病的新基因座和机制提供所需的见解。这项研究通过果蝇和人类遗传学实验室之间的合作，提供了果蝇和人类之间的快速翻译。

DESCRIPTION (provided by applicant): Genetic defects that lead to photoreceptor cell death in age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are highly heterogeneous and now include a list of more than 132 genes. Using Drosophila as a molecular genetic model for unraveling genetic loci in retinal degeneration disorders, such as AMD and RP, we have recently identified an entirely new class of molecules that are critical to photoreceptor viability and cell function. This is a class of sodium dependent symporters or co-transporters that move small molecules across membranes in exchange for sodium. Photoreceptors in Drosophila and humans alike possess several transport systems such as the sodium/calcium (-potassium) exchangers (NCKX) and the ABC transporters. Based on these and other similarities between Drosophila and human visual systems, we propose that the sodium dependent transporters may be critical loci in certain genetically inherited forms of human retinal degeneration. Mutations in the sodium dependent co-transporter lead to photoreceptor pathology and age-related retinal degeneration in Drosophila. In addition, these mutations also cause defects in the molecular weight of rhodopsin. We propose a link between the sodium dependent co-transporter and rhodopsin. In many cases, sodium dependent co-transporters are critical in protecting cells against oxidative damage. Oxidative damage is thought to contribute to AMD and RP as well as diabetic retinopathy. Therefore, sodium dependent transporters may be important loci in some forms of retinal degeneration. Unmasking novel classes of molecules opens up whole new areas of research as well as the development of new therapeutic strategies. Our data continue to support the concept that studies in Drosophila are highly valuable for uncovering the basis of retinal degeneration in humans. Drosophila offers quick insight into new classes of proteins that are strong candidates for photoreceptor function and retinal disease. The high impact and innovation in this application is to utilize the power of Drosophila molecular genetics to provide needed insights into novel loci and mechanisms in retinal degeneration disease. This study provides a rapid translation between Drosophila and humans through collaboration between Drosophila and human genetics laboratories.