P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

Meihui He; Mingfang Xia; Qian Yang; Xingyi Chen; Haibo Li; Xiaobo Xia

doi:10.4103/1673-5374.389646

P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

Neural Regen Res. 2024 Aug 1;19(8):1849-1856. doi: 10.4103/1673-5374.389646. Epub 2023 Dec 11.

Authors

Meihui He^{1

2

3}, Mingfang Xia^{1

2

3}, Qian Yang^{1

2

3}, Xingyi Chen^{1

2

3}, Haibo Li^{1

2

3}, Xiaobo Xia^{1

2

3}

Affiliations

¹ Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
² Hunan Key Laboratory of Ophthalmology, Changsha, Hunan Province, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Abstract

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.

Grants and funding

Funding:This work was supported by the National Natural Science Foundation of China, Nos. 81974134 (to XX) and 82000895 (to HL); National Key Research and Development Program of China, Nos. 2021YFA1101200 & 2021YFA1101202; and National Natural Science Foundation of Hunan Province, China, No. 2022JJ30071 (to HL).