Li Panpan, Shi Xin, Liu Hanhan, Feng Yuan, Wang Xiaosha, Herb Marc, Ji Haichao, Wagner Stefan, Vogt Johannes, Prokosch Verena
Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50937, Germany.
Key Laboratory of Yunnan Province, Yunnan Eye Institute, Affiliated Hospital of Yunnan University, Yunnan University, Kunming, 650021, China.
Neurosci Bull. 2025 Jun 2. doi: 10.1007/s12264-025-01417-0.
Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
尽管青光眼患者的眼内压（IOP）得到了有效控制，但神经元损伤仍持续存在，因此需要针对视网膜神经节细胞（RGC）的神经保护策略。在本研究中，我们研究了γ-羟基丁酸类似物HOCPCA在青光眼模型中的神经保护作用，重点关注其对CaMKII信号传导、氧化应激和神经炎症反应的影响。通过蛋白质组学分析高眼压动物模型的视网膜组织。体外培养的小鼠视网膜外植体先承受压力升高和氧化应激，然后进行HOCPCA处理。HOCPCA显著减轻了氧化应激和压力升高诱导的RGC损失，保留了神经元功能。它恢复了CaMKIIα和β的水平，维持了RGC的完整性，同时还调节了氧化应激和神经炎症反应。这些发现表明，HOCPCA通过与CaMKII相互作用，有望成为青光眼的神经保护疗法。
