Department of Ophthalmology and Visual Sciences, West Virginia University, Morgantown, WV, 26506, USA.
Department of Biochemistry, West Virginia University, Morgantown, WV, 26506, USA.
Amino Acids. 2021 Dec;53(12):1789-1806. doi: 10.1007/s00726-021-02981-1. Epub 2021 Apr 19.
The retina is one of the most energy-demanding tissues in the human body. Photoreceptors in the outer retina rely on nutrient support from the neighboring retinal pigment epithelium (RPE), a monolayer of epithelial cells that separate the retina and choroidal blood supply. RPE dysfunction or cell death can result in photoreceptor degeneration, leading to blindness in retinal degenerative diseases including some inherited retinal degenerations and age-related macular degeneration (AMD). In addition to having ready access to rich nutrients from blood, the RPE is also supplied with lactate from adjacent photoreceptors. Moreover, RPE can phagocytose lipid-rich outer segments for degradation and recycling on a daily basis. Recent studies show RPE cells prefer proline as a major metabolic substrate, and they are highly enriched for the proline transporter, SLC6A20. In contrast, dysfunctional or poorly differentiated RPE fails to utilize proline. RPE uses proline to fuel mitochondrial metabolism, synthesize amino acids, build the extracellular matrix, fight against oxidative stress, and sustain differentiation. Remarkably, the neural retina rarely imports proline directly, but it uptakes and utilizes intermediates and amino acids derived from proline catabolism in the RPE. Mutations of genes in proline metabolism are associated with retinal degenerative diseases, and proline supplementation is reported to improve RPE-initiated vision loss. This review will cover proline metabolism in RPE and highlight the importance of proline transport and utilization in maintaining retinal metabolism and health.
视网膜是人体中能量需求最高的组织之一。外视网膜中的光感受器依赖于相邻的视网膜色素上皮（RPE）的营养支持，RPE 是一层上皮细胞，将视网膜与脉络膜血液供应分开。RPE 功能障碍或细胞死亡可导致光感受器变性，导致包括一些遗传性视网膜变性和年龄相关性黄斑变性（AMD）在内的视网膜退行性疾病失明。除了可以从血液中获得丰富的营养物质外，RPE 还从相邻的光感受器获得乳酸。此外，RPE 可以每天吞噬富含脂质的外节进行降解和再循环。最近的研究表明，RPE 细胞优先将脯氨酸作为主要代谢底物，并且它们富含脯氨酸转运蛋白 SLC6A20。相比之下，功能失调或分化不良的 RPE 无法利用脯氨酸。RPE 利用脯氨酸为线粒体代谢提供燃料，合成氨基酸，构建细胞外基质，抵抗氧化应激，并维持分化。值得注意的是，神经视网膜很少直接摄取脯氨酸，但它可以摄取和利用 RPE 中脯氨酸分解代谢产生的中间产物和氨基酸。脯氨酸代谢基因的突变与视网膜退行性疾病有关，并且据报道脯氨酸补充可以改善由 RPE 引发的视力丧失。本综述将涵盖 RPE 中的脯氨酸代谢，并强调脯氨酸转运和利用在维持视网膜代谢和健康方面的重要性。
