He Meihui, Xia Mingfang, Yang Qian, Chen Xingyi, Li Haibo, Xia Xiaobo
Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Hunan Key Laboratory of Ophthalmology, Changsha, Hunan Province, China.
Neural Regen Res. 2024 Aug 1;19(8):1849-1856. doi: 10.4103/1673-5374.389646. Epub 2023 Dec 11.
JOURNAL/nrgr/04.03/01300535-202408000-00040/figure1/v/2023-12-16T180322Z/r/image-tiff The retina of zebrafish can regenerate completely after injury. Multiple studies have demonstrated that metabolic alterations occur during retinal damage; however to date no study has identified a link between metabolites and retinal regeneration of zebrafish. Here, we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration. Among the differentially-expressed metabolites, we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish. Then, we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish. Importantly, p-aminobenzoic acid activated Achaetescute complex-like 1a expression, thereby promoting Müller glia reprogramming and division, as well as Müller glia-derived progenitor cell proliferation. Finally, we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution. Taken together, these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.
《期刊》/nrgr/04.03/01300535 - 202408000 - 00040/图1/v/2023 - 12 - 16T180322Z/图像 - 标签图像文件格式 斑马鱼的视网膜在受伤后能够完全再生。多项研究表明，视网膜损伤期间会发生代谢改变；然而，迄今为止，尚无研究确定代谢物与斑马鱼视网膜再生之间的联系。在此，我们对N - 甲基 - D - 天冬氨酸损伤的斑马鱼视网膜进行了非靶向代谢组测序，以阐明视网膜再生的代谢组学机制。在差异表达的代谢物中，我们发现斑马鱼N - 甲基 - D - 天冬氨酸损伤的视网膜中对氨基苯甲酸显著减少。然后，我们研究了对氨基苯甲酸在成年斑马鱼视网膜再生中的作用。重要的是，对氨基苯甲酸激活了类无翅型 - 无触角型复合体样1a的表达，从而促进了穆勒胶质细胞的重编程和分裂，以及穆勒胶质细胞衍生的祖细胞增殖。最后，我们排除了叶酸和炎症作为对氨基苯甲酸的下游效应物，并证明对氨基苯甲酸对穆勒胶质细胞分布影响不大。综上所述，这些发现表明，对氨基苯甲酸通过激活斑马鱼N - 甲基 - D - 天冬氨酸损伤视网膜中的类无翅型 - 无触角型复合体样1a表达，促进视网膜再生。
