年龄相关性黄斑变性（AMD）是一种与衰老相关的多因素退行性疾病，炎症、免疫与其发病密切相关。玻璃膜疣（drusen）的发生发展被认为是AMD形成的标志，而视网膜色素上皮细胞（RPE）的氧化损伤在玻璃膜疣发生发展中起了关键作用。人 RGR（RPE retinal G protein-coupled receptor）是一种位于RPE细胞和Müller细胞上的跨膜蛋白，对于神经视网膜的存活和正常功能发挥起重要作用。人类RGR基因突变（RGR-d）可导致视网膜色素变性或周围脉络膜脉络膜萎缩，然而RGR-d与AMD尤其是与玻璃膜疣形成的关联尚不明确。本研究拟通过在培养的RPE细胞导入RGR-d基因突变以及体内RGR-d敲除的小鼠动物模型来探求RGR-d在亚细胞水平的具体位置、与玻璃膜疣形成的关系及对蛋白异常降解的影响，以明确RGR-d在AMD发病机制中的作用，为AMD的治疗提供新的思路。

Age-related macular degeneration belongs to a multifactorial neurodegenerative disease associated with aging; inflammation and immune response are closely involved in the onset and progression of this disease. During the development of AMD, retinal pigment epithelium (RPE) oxidative damage plays a important role in the development of AMD, and the development of drusen is commonly thought to be the key event. The human RGR (RPE retinal G protein-coupled receptor) gene encodes a transmembrane protein that is located in the RPE cells and Müller cells. When activated by light, RGR protein converts all-trans-retinal stereospecifically to its 11-cis isomer. RGR is pivotal for health, viability and normal functioning of the neuroretina. During the transcription and translation of human RGR gene, splice variat (RGR-d) of its mRNA was identified, RGR-d, exists in almost all persons. So far the specific mechanism about the splice variant in protein abnormal degradation and transferring pathway is not clear. We are going to generate the RGR-d mutant in cell culture in vitro and a mouse model with RGR-d knock-in to study the subcellular localization of RGR-d protein, and its relation with the drusen, exsomoe pathway and protein aberrant degradation. Through which the role of splice variant of RGR-d in AMD will be elucidated, to shed light new ideas and ways for treatment of AMD.