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Abstract #26331 Published in IGR 12-3
Preconditioning with inhalative carbon monoxide protects rat retinal ganglion cells from ischemia/reperfusion injury
Biermann J; Lagrèze WA; Dimitriu C; Stoykow C; Goebel UInvestigative Ophthalmology and Visual Science 2010; 51: 3784-3791
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.
University Eye Hospital Freiburg, University Medical Center, Killianstrasse 5, 79106 Freiburg, Germany. julia.biermann@uniklinik-freiburg.de
Classification:
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
