Li Bo, Zhang Ting, Liu Wei, Wang Yekai, Xu Rong, Zeng Shaoxue, Zhang Rui, Zhu Siyan, Gillies Mark C, Zhu Ling, Du Jianhai
Departments of Ophthalmology and Biochemistry, West Virginia University, WVU Eye Institute, One Medical Center Dr, PO Box 9193, Morgantown, WV 26506, USA.
Department of Ophthalmology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu Province 225100, China.
iScience. 2020 Oct 14;23(11):101672. doi: 10.1016/j.isci.2020.101672. eCollection 2020 Nov 20.
Photoreceptors, especially cones, which are enriched in the human macula, have high energy demands, making them vulnerable to metabolic stress. Metabolic dysfunction of photoreceptors and their supporting retinal pigment epithelium (RPE) is an important underlying cause of degenerative retinal diseases. However, how cones and the macula support their exorbitant metabolic demand and communicate with RPE is unclear. By profiling metabolite uptake and release and analyzing metabolic genes, we have found cone-rich retinas and human macula share specific metabolic features with upregulated pathways in pyruvate metabolism, mitochondrial TCA cycle, and lipid synthesis. Human neural retina and RPE have distinct but complementary metabolic features. Retinal metabolism centers on NADH production and neurotransmitter biosynthesis. The retina needs aspartate to sustain its aerobic glycolysis and mitochondrial metabolism. RPE metabolism is directed toward NADPH production and biosynthesis of acetyl-rich metabolites, serine, and others. RPE consumes multiple nutrients, including proline, to produce metabolites for the retina.
光感受器，尤其是在人类黄斑中富集的视锥细胞，对能量需求很高，这使得它们容易受到代谢应激的影响。光感受器及其支持性视网膜色素上皮（RPE）的代谢功能障碍是视网膜退行性疾病的一个重要潜在原因。然而，视锥细胞和黄斑如何满足其过高的代谢需求以及与RPE进行通信尚不清楚。通过分析代谢物的摄取和释放并分析代谢基因，我们发现富含视锥细胞的视网膜和人类黄斑具有特定的代谢特征，丙酮酸代谢、线粒体三羧酸循环和脂质合成中的途径上调。人类神经视网膜和RPE具有不同但互补的代谢特征。视网膜代谢以NADH产生和神经递质生物合成为中心。视网膜需要天冬氨酸来维持其有氧糖酵解和线粒体代谢。RPE代谢则指向NADPH产生以及富含乙酰的代谢物、丝氨酸等的生物合成。RPE消耗多种营养物质，包括脯氨酸，以产生供视网膜使用的代谢物。
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