Hydrogen sulfide supplement preserves mitochondrial function of retinal ganglion cell in a rat glaucoma model

Abstract

Glaucoma is a neurodegenerative disease of visual system characterized by gradual loss of retinal ganglion cells (RGC). Since mitochondrial dysfunction of RGC is significantly involved in the pathological mechanisms of glaucoma, and hydrogen sulfide (H₂S) takes part in the pathogeny of glaucoma and shows promising potential in restoring mitochondrial function in other neurons, the authors aimed to investigate the impact of H₂S on mitochondrial function of RGC with a rat glaucoma model. An established chronic ocular hypertension (COH) rat model induced by injection of cross-linking hydrogel into anterior chamber was adopted, and a H₂S donor, sodium hydrosulfide (NaHS), was selected to treat rats through intraperitoneal injection. After a period of 4 weeks, RGCs were isolated from the subjected rats with an immunopanning method and went through evaluations of mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, intracellular Ca2 + level, reactive oxygen species (ROS) level, and cytosolic Cytochrome C distribution. The results showed that the mitochondrial function of RGC in experimental glaucoma was markedly improved by H₂S supplement, being presented as stabilization of MMP, alleviation of MPTP opening, improvement of intracellular Ca²⁺ hemostasis, reduction of ROS accumulation, and inhibition of Cytochrome C release. Our study implicated that preservation of mitochondrial function by H₂S probably plays a key role in protecting RGC in the context of glaucomatous neuropathy, and it is worth further deepgoing research to benefit the development of glaucoma treatment.

Keywords: Chronic ocular hypertension; Gasotransmitter; Glaucomatous neuropathy; Mitochondria dysfunction; Optic neuroprotection.