Methane rescues retinal ganglion cells and limits retinal mitochondrial dysfunction following optic nerve crush.
Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC. The retinal ganglion cells (RGCs) density was assessed by hematoxylin and eosin staining and Fluoro-Gold retrogradely labeling. Visual function was evaluated by flash visual evoked potentials (FVEP). The retinal apoptosis was measured by terminal-deoxy-transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of apoptosis-related factors, such as phosphorylated Bcl-2-associated death promoter (pBAD), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Bcl-2 associated X protein (Bax) and Bcl-2 extra large (Bcl-xL). Retinal mitochondrial function was assessed by the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), the mitochondrial DNA (mtDNA) copy number, citrate synthase activity and ATP content. Methane treatment significantly improved the RGC loss and visual dysfunction following ONC. As expected, methane also remarkably inhibited the retinal neural apoptosis, such as the fewer TUNEL-positive cells in ganglion cell layer, accompanied by the up-regulations of anti-apoptotic factors (pGSK-3β, pBAD, Bcl-xL) and the down-regulation of pro-apoptotic factor (Bax). Furthermore, methane treatment suppressed up-regulations of critical mitochondrial components (PGC-1α, NRF1 and TFAM) mRNA and mtDNA copy number, as well as improved the reduction of functional mitochondria markers, including citrate synthase activity and ATP content, in retinas with ONC. Taken together, methane treatment promotes RGC survival and limits retinal mitochondrial dysfunction against ONC insult. Methane can be a potential neuroprotective agent for traumatic and glaucomatous neurodegeneration.
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ruobing
R
Wang
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Qinglei
Q
Sun
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Fangzhou
F
Xia
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Zeli
Z
Chen
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Jiangchun
J
Wu
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yuelu
Y
Zhang
Department of Anatomy, Second Military Medical University, Shanghai, China. Electronic address: xujiajun1963@126.com.
Jiajun
J
Xu
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: liulin1963rj@126.com.
Lin
L
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D008697:Methane / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D009900:Optic Nerve / Q000187:drug effects; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
D008697:Methane
Anti-apoptosis; Methane; Mitochondrial dysfunction; Optic nerve crush; Retinal ganglion cell