Preconditioning with Inhalative Carbon Monoxide Protects Rat Retinal Ganglion Cells from Ischemia/Reperfusion Injury

Abstract

PURPOSE. Retinal ischemia/reperfusion (I/R) injury damages retinal neurons. Carbon monoxide (CO) recently attracted attention as cytoprotective because of its anti-inflammatory and antiapoptotic effects. Rapid preconditioning of retinal neurons by inhaled CO before I/R injury may reduce inflammation and apoptosis in retinal ganglion cells (RGCs). METHODS. I/R injury was performed on the left eyes of rats (n = 8) with or without inhaled CO preconditioning (250 ppm) for 1 hour before ischemia. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Retinal tissue was further harvested to analyze protein expression of TNF-alpha, HSP-70, and mitogen-activated protein kinases (MAPKs) pERK1/2 and p-p38. DNA-binding activities of the transcription factors NF-kappaB, AP-1, CREB, and HSF-1 were determined to elucidate a possible pathway of neuroprotection. RESULTS. Seven days after I/R injury, RGC death decreased by 52% in the CO preconditioning group compared with controls receiving room air (P < 0.001). Similarly, CO inhalation resulted in attenuated caspase-3 activity and TNF-alpha protein expression. In contrast, HSP-70 protein expression was elevated in the retina after CO. CREB and HSF-1 showed CO-dependent regulation and p-p38 MAPK. CONCLUSIONS. Rapid preconditioning with CO mediates anti-inflammatory and antiapoptotic effects in retinal I/R injury, thus making it neuroprotective. Further studies are needed to evaluate whether CO posttreatment may represent a therapeutic option counteracting ischemic neuronal injury.

Chitosan oligosaccharides prevented retinal ischemia and reperfusion injury via reduced oxidative stress and inflammation in rats

“…Nitric oxide (NO) is generated by iNOS-induced delayed neuronal cell death after ischemia (Samdani et al, 1997). It had been reported that the activation of NF-kB is associated with an increased expression of these inflammatory mediators after I/R injury (Dvoriantchikova et al, 2009a(Dvoriantchikova et al, , 2009bGustavsson et al, 2008;Biermann et al, 2010). In this study, we clearly demonstrated that COS could inhibit NF-kB activation and decrease the expression of IL-1b, TNF-a, MCP-1, iNOS and ICAM-1.…”

Hydrogen-rich saline reduces cell death through inhibition of DNA oxidative stress and overactivation of poly (ADP-ribose) polymerase-1 in retinal ischemia-reperfusion injury

“…By contrast, retinas with RIR injury experienced severe cell death in the GCL 7 days after reperfusion, which was in accordance with previous studies (22,23). Treatment with HRS significantly decreased the number of TUNEL-positive cells in the GCL of RIR rats on the seventh day after reperfusion (P<0.001), suggesting that HRS may have a protective effect on cell apoptosis (Fig.…”

Mitochondrial Quality Control as a Therapeutic Target

“…Prior to this understanding, there was controversy over the incontrovertible toxicity of the gas versus observations supporting low dose CO as a cell protectant operating through general anti-inflammatory and antiapoptotic properties (Ryter et al, 2006;Suliman and Piantadosi, 2014). Indeed, many protective effects of HO-1 induction by ischemia, hypoxia, oxidative stress, metals, and inflammation are not simply due to heme clearance and in many cases can be recapitulated by CO administration (Maines, 2005;Vieira et al, 2008;Biermann et al, 2010;Lee et al, 2014).…”