Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival

Autor: Jialiang, Yang, Yuhong, Chen, Tongdan, Zou, Bai, Xue, Fang, Yang, Xiangzhou, Wang, Yibo, Huo, Boyun, Yan, Yuxia, Xu, Shiyu, He, Yi, Yin, Jing, Wang, Xiong, Zhu, Lin, Zhang, Yu, Zhou, Zhengfu, Tai, Ping, Shuai, Man, Yu, Qian, Luo, Yilian, Cheng, Bo, Gong, Xianjun, Zhu, Jing, Zhang, Xinghuai, Sun, Ying, Lin, Houbin, Zhang, Zhenglin, Yang
Rok vydání: 2022
Předmět:
Zdroj: Science China Life Sciences. 66:211-225
ISSN: 1869-1889
1674-7305
DOI: 10.1007/s11427-021-2126-2
Popis: Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1
Databáze: OpenAIRE