Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
Adv Exp Med Biol. 2019;1185:15-19. doi: 10.1007/978-3-030-27378-1_3.
Age-related macular degeneration (AMD) is the most common cause of irreversible blindness. We do not know the cause of the disease and have inadequate prevention and treatment strategies for those at risk or affected. The greatest risk factors include age and race, with the white population at the highest risk for the disease. We developed the hypothesis that pigmentation in the retinal pigment epithelium (RPE) protects darkly pigmented individuals from AMD. We have tested this hypothesis in multiple ways including dissecting the pigmentation pathway in RPE using albinism-related tools, identification of a G protein-coupled receptor in the pigmentation pathway that drives expression of trophic factors, and using a very large retrospective chart analysis to test whether the ligand for the receptor prevents AMD. In total, our results indicate that pigmentation of the RPE is a cornerstone of RPE-retinal interaction and support and that the receptor in the pigmentation pathway most likely underlies the racial bias of the disease. The ligand for that receptor is an ideal candidate as a preventative and treatment for AMD. Here we summarize these results, discussing the research in its entirety with one overall goal, treatment or prevention of AMD.
年龄相关性黄斑变性（AMD）是不可逆性失明的最常见原因。我们不知道这种疾病的病因，也没有针对高危人群或患者的充分预防和治疗策略。最大的风险因素包括年龄和种族，其中白种人患病风险最高。我们提出了一个假设，即视网膜色素上皮（RPE）中的色素沉着可以保护深色色素沉着的个体免受 AMD 的侵害。我们已经通过多种方式验证了这一假设，包括使用与白化病相关的工具来剖析 RPE 中的色素沉着途径，鉴定出在色素沉着途径中驱动营养因子表达的 G 蛋白偶联受体，以及使用非常大的回顾性图表分析来测试该受体的配体是否可以预防 AMD。总的来说，我们的结果表明，RPE 的色素沉着是 RPE-视网膜相互作用的基石，并支持该色素沉着途径中的受体很可能是该疾病的种族偏见的基础。该受体的配体是作为 AMD 预防和治疗的理想候选物。在这里，我们总结了这些结果，全面讨论了这项研究，其总体目标是治疗或预防 AMD。
