Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, Shandong, 266071, China.
Department of Urology, Qingdao Municipal Hospital Affiliated to Qingdao Medical College of Qingdao University, Qingdao, Shandong, 266071, China.
Exp Eye Res. 2024 Apr;241:109853. doi: 10.1016/j.exer.2024.109853. Epub 2024 Mar 5.
High myopia is a risk factor for primary open angle glaucoma (POAG). The pathological mechanism of high myopia induced POAG occurrence is not fully understood. In this study, we successfully established the guinea pig model of ocular hypertension with high myopia, and demonstrated the susceptibility of high myopia for the occurrence of microbead-induced glaucoma compared with non-myopia group and the effect of YAP/TGF-β signaling pathway in TM pathogenesis induced by high myopia. Moreover, we performed stretching treatment on primary trabecular meshwork (TM) cells to simulate the mechanical environment of high myopia. It was found that stretching treatment disrupted the cytoskeleton, decreased phagocytic function, enhanced ECM remodeling, and promoted cell apoptosis. The experiments of mechanics-induced human TM cell lines appeared the similar trend. Mechanically, the differential expressed genes of TM cells caused by stretch treatment enriched YAP/TGF-β signaling pathway. To inhibit YAP/TGF-β signaling pathway effectively reversed mechanics-induced TM damage. Together, this study enriches mechanistic insights of high myopia induced POAG susceptibility and provides a potential target for the prevention of POAG with high myopia.
高度近视是原发性开角型青光眼（POAG）的一个危险因素。高度近视导致 POAG 发生的病理机制尚未完全阐明。在这项研究中，我们成功建立了伴有高度近视的豚鼠眼高压模型，与非近视组相比，证实了高度近视对微珠诱导性青光眼发生的易感性，以及 YAP/TGF-β 信号通路在高度近视诱导的 TM 发病机制中的作用。此外，我们对原代小梁细胞进行拉伸处理，模拟高度近视的力学环境。结果发现，拉伸处理破坏了细胞骨架，降低了吞噬功能，增强了细胞外基质重塑，促进了细胞凋亡。人 TM 细胞系的力学实验也出现了类似的趋势。在力学上，拉伸处理引起的 TM 细胞差异表达基因富集了 YAP/TGF-β 信号通路。有效地抑制 YAP/TGF-β 信号通路可以逆转力学诱导的 TM 损伤。总之，这项研究丰富了高度近视导致 POAG 易感性的机制见解，并为预防高度近视性 POAG 提供了一个潜在的靶点。
