title: Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.
abstract: Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance.
authors.affiliation: Department of Histology and Embryology, Taishan Medical University, Taian 271000, Shandong, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Ge
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Shi
authors.forename: Changqing
authors.initials: C
authors.lastname: Du
authors.forename: Hui
authors.initials: H
authors.lastname: Du
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D019610:Cytoprotection; D000091342:Endoplasmic Reticulum Chaperone BiP; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D006168:Guinea Pigs; D006360:Heat-Shock Proteins; D006859:Hydrogen; D058449:Intravitreal Injections; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010529:Peritoneal Cavity; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D000091342:Endoplasmic Reticulum Chaperone BiP; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D018698:Glutamic Acid; D012965:Sodium Chloride; D006859:Hydrogen; D052247:Nitric Oxide Synthase Type II