Yang Ming, Bian Fuyun, Feng Xue, Li Liang, Huang Haoliang, Liu Liang, Dalal Roopa, Yang Hang, Suraparaju Pranav Varma, Cao Frank, Ong Petrina, Luo Alexandria, Liu Dong, Hu Yang
Spencer Center for Vision Research, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Dougherty Valley High School, San Ramon (12th grade), California, United States.
bioRxiv. 2025 Jun 6:2025.06.03.657677. doi: 10.1101/2025.06.03.657677.
Preventing retinal ganglion cells (RGCs)'s soma and axon degeneration and promoting optic nerve (ON) regeneration holds great promise for effective glaucoma treatment. To explore potential neural repair strategies, we focused on glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation. GPX4 is upregulated in surviving RGCs after acute ON crush or chronic ocular hypertension insult, and also in regenerating RGCs. AAV-mediated RGC-specific overexpression of GPX4 promotes significant ON regeneration and RGC survival, along with visual functional preservation, demonstrating the detrimental role of lipid peroxidation in glaucoma and the therapeutic potential of modulating lipid peroxidation through GPX4 in optic neuropathies.
预防视网膜神经节细胞（RGCs）的胞体和轴突退化并促进视神经（ON）再生，对青光眼的有效治疗具有巨大潜力。为了探索潜在的神经修复策略，我们聚焦于谷胱甘肽过氧化物酶4（GPX4），它是脂质过氧化的关键调节因子。在急性视神经挤压或慢性高眼压损伤后存活的RGCs中，以及在再生的RGCs中，GPX4均上调。腺相关病毒（AAV）介导的RGC特异性过表达GPX4可促进显著的视神经再生和RGC存活，同时保留视觉功能，这表明脂质过氧化在青光眼中的有害作用，以及通过GPX4调节脂质过氧化在视神经病变中的治疗潜力。
