Biomaterial Database

Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues. 2024

Jian Wu, and Chaoye Wang, and Shuhui Sun, and Tianmin Ren, and Lijie Pan, and Hongyi Liu, and Simeng Hou, and Shen Wu, and Xuejing Yan, and Jingxue Zhang, and Xiaofang Zhao, and Weihai Liu, and Sirui Zhu, and Shuwen Wei, and Chi Zhang, and Xu Jia, and Qi Zhang, and Ziyu Yu, and Yehong Zhuo, and Qi Zhao, and Chenlong Yang, and Ningli Wang

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100730, China.

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.