title: Low-dose carbon monoxide inhalation protects neuronal cells from apoptosis after optic nerve crush.
abstract: Glaucomatous optic neuropathy, including axonal degeneration and apoptotic death of retinal ganglion cells (RGCs), eventually leads to irreversible visual impairment. Carbon monoxide (CO) acts as a therapeutic agent against neural injury via its anti-apoptotic effect. Here we hypothesized that low-dose CO inhalation can protect RGCs in a rat model of optic nerve crush (ONC). ONC was performed on adult male Sprague Dawley rats to imitate glaucomatous optic damage. Low-dose CO (250 ppm) or air was inhaled for 1 h immediately after ONC, and all the tests were carried out 2 weeks later. Flash visual evoked potentials (FVEP) and pupil light relax (PLR) were recorded for the assessment of visual function. RGC density was evaluated by hematoxylin and eosin staining and Fluorogold labeling. Retinal apoptotic process was assessed by TUNEL staining and caspase-3 activity measurement. Low-dose CO treatment significantly ameliorated the abnormalities of FVEP and PLR induced by ONC. As expected, the RGC density was increased remarkably by CO inhalation after the glaucomatous optic nerve insult. Moreover, CO treatment after ONC significantly decreased the number of TUNEL-positive cells in ganglion cell layer and attenuated the retinal caspase-3 activity. Low-dose CO inhalation protects RGCs from optic nerve injury via inhibiting caspase-3 dependent apoptosis.
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anatomy, Second Military Medical University, Shanghai, China.
authors.forename: Zeli
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anatomy, Second Military Medical University, Shanghai, China.
authors.forename: Jiangchun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anatomy, Second Military Medical University, Shanghai, China.
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Anatomy, Second Military Medical University, Shanghai, China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Second Military Medical University, Shanghai, China. Electronic address: xujiajun1963@126.com.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: liulin1963rj@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D020221:Optic Nerve Injuries / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D002248:Carbon Monoxide
keywords: Apoptosis; Carbon monoxide; Flash visual evoked potentials; Optic nerve crush; Retina ganglion cell