Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, United Kingdom.
Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, United Kingdom; Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi Arabia.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Jul;1866(7):158927. doi: 10.1016/j.bbalip.2021.158927. Epub 2021 Mar 24.
Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.
年龄相关性黄斑变性（AMD）是老年人最常见的视力障碍原因，随着年龄的增长可能导致完全失明。AMD 的主要临床特征是视网膜色素上皮（RPE）细胞下方存在富含胆固醇的沉积物。这些沉积物会引发氧化应激和炎症。有研究表明，胆固醇代谢失衡与 AMD 的发病机制有关。然而，胆固醇代谢失衡在 AMD 中的功能作用仍不清楚。STARD 蛋白是一类含有甾体急性调节蛋白相关脂转移结构域的蛋白。哺乳动物中有 15 种 STARD 蛋白，其中一些如 STARD3，负责胆固醇的运输。以前，STARD 蛋白在视网膜胆固醇代谢和运输方面的研究尚未开展。在这里，我们检测了 Stard3 基因在 2 月龄和 20 月龄小鼠视网膜和 RPE 细胞中的表达。我们发现，与 2 月龄相比，20 月龄时小鼠 RPE 和视网膜中 Stard3 基因转录本的表达明显降低。我们构建了一个稳定过表达 STARD3 的 ARPE-19 细胞系，发现这导致胆固醇外排增加，细胞内氧化 LDL 积累减少，抗氧化能力增强，炎症细胞因子水平降低。数据表明，STARD3 通过促进细胞内胆固醇的清除和减缓疾病进展，可能成为 AMD 的一个潜在靶点。
