Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimics events occurring in human glaucoma. Senescence‐related chromatin remodeling leads to profound transcriptional changes including the upregulation of a subset of genes that encode multiple proteins collectively referred to as the senescence‐associated secretory phenotype (SASP). Emerging evidence suggests that the presence of these proinflammatory and matrix‐degrading molecules has deleterious effects in a variety of tissues. In the current study, we demonstrated in a transgenic mouse model that early removal of senescent cells induced upon elevated intraocular pressure (IOP) protects unaffected RGCs from senescence and apoptosis. Visual evoked potential (VEP) analysis demonstrated that remaining RGCs are functional and that the treatment protected visual functions. Finally, removal of endogenous senescent retinal cells after IOP elevation by a treatment with senolytic drug dasatinib prevented loss of retinal functions and cellular structure. Senolytic drugs may have the potential to mitigate the deleterious impact of elevated IOP on RGC survival in glaucoma and other optic neuropathies.

中文翻译：

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在实验性高眼压症中及早去除衰老细胞可保护视网膜神经节细胞的丢失。

实验性高眼压会诱发视网膜神经节细胞（RGC）的衰老，从而模仿人类青光眼中发生的事件。衰老相关的染色质重塑导致深刻的转录变化，包括上调编码多种蛋白质的基因子集的上调，这些基因统称为衰老相关的分泌表型（SASP）。新兴证据表明，这些促炎和降解基质的分子的存在对多种组织具有有害作用。在当前的研究中，我们在转基因小鼠模型中证明了眼内压升高（IOP）引起的早期去除衰老细胞可以保护未受影响的RGC免受衰老和凋亡的影响。视觉诱发电位（VEP）分析表明，剩余的RGC具有功能，并且治疗可保护视觉功能。最后，在眼压升高后，通过使用溶酶药物达沙替尼治疗去除内源性衰老视网膜细胞可以防止视网膜功能和细胞结构的丧失。缓溶药可能具有减轻IOP升高对青光眼和其他视神经病变RGC存活的有害影响的潜力。