Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ 85724, USA.
Cells. 2020 Apr 8;9(4):910. doi: 10.3390/cells9040910.
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.
年龄相关性黄斑变性(AMD)是全球导致不可逆性失明的主要原因。AMD 的发病风险随年龄增长而增加,在白种人群中最为常见。在这里,我们讨论了与种族、色素沉着和 AMD 易感性相关的因素的趋同,其中主要缺陷发生在视网膜支持细胞——视网膜色素上皮(RPE)中。我们探讨了 AMD 发病率中观察到的种族偏见是否与种族之间色素沉着的基础水平存在固有差异有关,以及 RPE 中的色素沉着途径活性是否可以防止视网膜变性。更具体地说,我们探讨了色素沉着途径中的 G 蛋白偶联受体 GPR143 的下游信号转导活性是否可能是 AMD 种族偏见的基础,并可能成为预防该疾病的靶点。最后,我们总结了一项大型回顾性研究的过去发现,该研究调查了用 L-DOPA 刺激 GPR143、色素沉着途径与 AMD 之间的关系,以期帮助开发预防或治疗 AMD 的新方法。阅读本综述的读者将了解到 AMD 的种族偏见,这与 RPE 的功能有关。