title: Protective effects of methane-rich saline on diabetic retinopathy via anti-inflammation in a streptozotocin-induced diabetic rat model.
abstract: As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL1-β) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-α, IL-1β, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR-192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs.
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jiangchun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Navy Aeromedicine, Second Military Medical University, Shanghai, China.
authors.forename: Zhouheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Navy Aeromedicine, Second Military Medical University, Shanghai, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zeli
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: linliu@sh163.net.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001813:Blood-Retinal Barrier; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D008297:Male; D008697:Methane / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000737:chemistry / Q000494:pharmacology*; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D012965:Sodium Chloride; D013311:Streptozocin; D008697:Methane
keywords: Diabetic retinopathy; Inflammatory; Methane; MicroRNA; Microarray