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.

中文翻译：

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衰老猕猴眼部流出组织的单细胞转录组图谱。


小梁网 (TM) 的逐渐退化与年龄相关的眼部疾病（如原发性开角型青光眼）有关。然而，TM衰老过程的分子基础和生物学意义尚未完全阐明。在这里，我们建立了老年猕猴 TM 的动态单细胞转录组图谱，其中我们将流出组织分为 12 种细胞亚型，并将线粒体功能障碍确定为 TM 衰老的一个显着特征。此外，我们将TM细胞分为13个簇，并对第0簇进行了深入分析，该簇的老化得分最高，两组之间细胞比例变化最显着。最终，我们发现APOE基因是衰老过程中cluster 0中重要的差异表达基因，凸显了细胞迁移和细胞外基质调节以及TM功能之间的密切关系。我们的工作进一步证明，沉默APOE基因可以通过解除对PI3K-AKT通路的抑制并下调细胞外基质成分的表达来增加迁移并减少细胞凋亡，从而增加房水流出率并将眼压维持在正常范围内。我们的工作为未来青光眼的临床诊断和治疗提供了宝贵的见解。