小梁网
细胞外基质
转录组
生物
基因沉默
PI3K/AKT/mTOR通路
青光眼
基因表达谱
细胞生物学
CTGF公司
神经科学
遗传学
癌症研究
信号转导
生长因子
受体
基因表达
基因
作者
Jian Wu,Chaoye Wang,Shuhui Sun,Tianmin Ren,Lijie Pan,Hongyi Liu,Simeng Hou,Shen Wu,Xuejing Yan,Jingxue Zhang,Zhao Xiao-fang,Weihai Liu,Shumin Zhu,Shaofeng Wei,Chi Zhang,Jia Xu,Qi Zhang,Zhenzhu Yu,Yehong Zhuo,Qi Zhao,Chenlong Yang,Ke Wang
标识
DOI:10.1093/procel/pwad067
摘要
The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in- depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.
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