HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma
Panpan Li1,2 · Xin Shi1,3,4 · Hanhan Liu1 · Yuan Feng1 · Xiaosha Wang1 · Marc Herb5,6 · Haichao Ji7 · Stefan Wagner7 · Johannes Vogt7 · Verena Prokosch11 Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne 50937, Germany
2 Key Laboratory of Yunnan Province, Yunnan Eye Institute, Afliated Hospital of Yunnan University, Yunnan University, Kunming 650021, China
3 Department of Orthopedics, The First People’s Hospital of Yunnan Province, Kunming 650032, China
4 The Afliated Hospital of Kunming University of Science and Technology, Kunming 650032, China
5 Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne 50935, Germany
6 Cologne Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne 50931, Germany
7 Molecular and Translational Neurosciences, CECAD Cluster of Excellence, CMMC Center of Molecular Medicine Cologne, University of Cologne, Cologne 50931, Germany
Abstract
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.
Keywords
CaMKII; HOCPCA; RGCs; Glaucoma; Neuroprotection
