HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.
10.1007/s12264-025-01417-0
- Author:
Panpan LI
1
;
Xin SHI
1
;
Hanhan LIU
1
;
Yuan FENG
1
;
Xiaosha WANG
1
;
Marc HERB
2
;
Haichao JI
3
;
Stefan WAGNER
3
;
Johannes VOGT
3
;
Verena PROKOSCH
4
Author Information
1. Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50937, Germany.
2. Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50935, Germany.
3. Molecular and Translational Neurosciences, CECAD Cluster of Excellence, CMMC Center of Molecular Medicine Cologne, University of Cologne, Cologne, 50931, Germany.
4. Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, 50937, Germany. verena.prokosch@uk-koeln.de.
- Publication Type:Journal Article
- Keywords:
CaMKII;
Glaucoma;
HOCPCA;
Neuroprotection;
RGCs
- MeSH:
Animals;
Retinal Ganglion Cells/metabolism*;
Glaucoma/pathology*;
Oxidative Stress/drug effects*;
Neuroprotective Agents/pharmacology*;
Mice;
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*;
Mice, Inbred C57BL;
Disease Models, Animal;
Neuroinflammatory Diseases/drug therapy*;
Neuroprotection/drug effects*;
Male;
Intraocular Pressure/drug effects*
- From:
Neuroscience Bulletin
2025;41(8):1329-1346
- CountryChina
- Language:English
-
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.
