Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Redox Biol. 2023 Jun;62:102687. doi: 10.1016/j.redox.2023.102687. Epub 2023 Mar 21.
Glaucoma is a common neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) loss and visual field defects. Pathologically high intraocular pressure (ph-IOP) is an important risk factor for glaucoma, and it triggers molecularly distinct cascades that control RGC death and axonal degeneration. Dynamin-related protein 1 (Drp1)-mediated abnormalities in mitochondrial dynamics are involved in glaucoma pathogenesis; however, little is known about the precise pathways that regulate RGC injury and death. Here, we aimed to investigate the role of the ERK1/2-Drp1-reactive oxygen species (ROS) axis in RGC death and the relationship between Drp1-mediated mitochondrial dynamics and PANoptosis in ph-IOP injury. Our results suggest that inhibiting the ERK1/2-Drp1-ROS pathway is a potential therapeutic strategy for treating ph-IOP-induced injuries. Furthermore, inhibiting Drp1 can regulate RGC PANoptosis by modulating caspase3-dependent, nucleotide-binding oligomerization domain-like receptor-containing pyrin domain 3(NLRP3)-dependent, and receptor-interacting protein (RIP)-dependent pathways in the ph-IOP model. Overall, our findings provide new insights into possible protective interventions that could regulate mitochondrial dynamics to improve RGC survival.
青光眼是一种常见的神经退行性疾病，其特征是视网膜神经节细胞（RGC）进行性丧失和视野缺损。病理性高眼压（ph-IOP）是青光眼的一个重要危险因素，它触发了分子上不同的级联反应，控制着 RGC 死亡和轴突变性。与 dynamin 相关蛋白 1（Drp1）介导的线粒体动力学异常与青光眼的发病机制有关；然而，关于调节 RGC 损伤和死亡的确切途径知之甚少。在这里，我们旨在研究 ERK1/2-Drp1-活性氧（ROS）轴在 RGC 死亡中的作用以及 Drp1 介导的线粒体动力学与 ph-IOP 损伤中 PANoptosis 之间的关系。我们的研究结果表明，抑制 ERK1/2-Drp1-ROS 通路可能是治疗 ph-IOP 诱导损伤的一种潜在治疗策略。此外，抑制 Drp1 可以通过调节 caspase3 依赖性、核苷酸结合寡聚结构域样受体含有吡喃结构域 3（NLRP3）依赖性和受体相互作用蛋白（RIP）依赖性途径来调节 RGC PANoptosis 在 ph-IOP 模型中。总的来说，我们的研究结果为可能的保护干预措施提供了新的见解，这些措施可以调节线粒体动力学以提高 RGC 的存活率。
