The Neuroprotection Of Low Concentration Carbon Monoxide On Incomplete Injury Of Optic Nerve

The injuries to retinas are always irreversible as they are the extension of central nervous system.A variety of diseases such as glaucoma,diabetic retinopathy,agerelated macular degeneration can initiate neuropathy,resulting in retinal ganglion cell(RGC)degeneration and axons lesions and eventually leading to loss of vision.It refers that low concentrations carbon monoxide(CO)has been demonstrated strong anti-inflammatory,anti-proliferation,anti-apoptosis,decreasing immune response and rejection and neuroprotective effects in various experiments in vivo and in vitro,as the concentrations below the toxic dose of the gas.Due to the low concentration of carbon monoxide,security should be controlled,if its dose is good for the recovery of the nerve injury by CO inhalation,it is prospective for its application.Objective: To study the neuroprotection of low concentrations CO on optic nerve incomplete injury model.Methods: The optic nerve crush(ONC)was performed to produce incomplete optic nerve injury model.Models randomly divided into ONC+CO group and ONC group,the ONC+CO group received 250 ppm CO inhalation for 1 h immediately after the operation.There was another group received sham-operated as the negative control.Flash visual evoked potential(FVEP)and pupillary light reflex(PLR)were tested to evaluate visual function two weeks later.We observed the retinal morphological changes using HE staining and FG labeling.In order to explore the apoptotic pathway in CO-induced protective effects on optic nerve injury,TUNEL staining of apoptotic cells and caspase-3 activity in retina were measured.Results: ONC injury had significantly impaired visual function and RGCs loss compared with the sham-operated animals.The low concentrations CO inhalation treatment significantly ameliorated the visual dysfunction by comparing the ONC+CO group and ONC group.The amplitude and latency of FVEP in ONC+CO group were 395.83 ± 172.52 μV and 148.04 ± 20.73 ms,which were significantly improved compared to the ONC group(amplitude 162.33 ± 70.47 μV,p < 0.05;latency 211.22 ± 19.56 ms,p < 0.001);PLR in ONC+CO group was more expeditious than that in ONC group.HE staining showed that the cell survival of GCL in ONC+CO group and ONC group were 65.3% and 48.2%(p < 0.001);the average density of fluorescent labeling of RGCs per square millimeter in ONC+CO group and ONC group were 2247.33 ± 232.30 and 1448.44 ± 290.91 respectively(p < 0.05).Low concentrations CO inhalation treatment significantly reduced TUNEL-positive cells in GCL and caspase-3 enzyme activity in retinas with ONC.Conclusion: Low concentrations CO inhalation ameliorated the visual dysfunction and improved the RGCs survival in a rat model of ONC.In addition,Low concentrations CO exerted neuroprotection on RGCs against optic nerve injury via inhibiting caspase-3 dependent apoptosis pathway.