Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury

• Published in: International journal of ophthalmology Vol. 17; no. 4; pp. 638 - 645
• Main Authors: Wu, Zhen-Kai, Zhu, You-Lin, Xiong, Meng-Qin, Zhong, Jing-Xiang
• Format: Journal Article
• Language: English
• Published: China International Journal of Ophthalmology Press 18.04.2024; Press of International Journal of Ophthalmology (IJO PRESS)
• Subjects: Basic Research; eicosane; glaucoma; metabolites; metabolites; glaucoma; eicosane
• ISSN: 2222-3959; 2227-4898
• DOI: 10.18240/ijo.2024.04.05

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.