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.
Keywords: Apoptosis; Carbon monoxide; Flash visual evoked potentials; Optic nerve crush; Retina ganglion cell.
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