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.

中文翻译：

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通过 YAP-TGFβ 针对力学引起的小梁网功能障碍改善高度近视引起的高眼压

高度近视是原发性开角型青光眼（POAG）的危险因素。高度近视引起POAG发生的病理机制尚不完全清楚。本研究成功建立了高度近视豚鼠模型，并论证了高度近视组与非近视组相比对微珠诱发青光眼发生的易感性以及YAP/TGF-β信号通路的影响高度近视引起的TM发病机制。此外，我们对原代小梁网（TM）细胞进行拉伸治疗，以模拟高度近视的机械环境。研究发现，拉伸治疗会破坏细胞骨架，降低吞噬功能，增强ECM重塑，促进细胞凋亡。力学诱导的人TM细胞系的实验也出现了类似的趋势。从机械角度来看，拉伸处理引起的TM细胞差异表达基因丰富了YAP/TGF-β信号通路。抑制YAP/TGF-β信号通路可有效逆转力学引起的TM损伤。总之，这项研究丰富了高度近视引起的 POAG 易感性的机制见解，并为预防高度近视的 POAG 提供了潜在的目标。