Proinsulin C-Peptide Attenuates Retinal Ischemia-Reperfusion Injury

Abstract

Abstract: : Purpose: C-peptide consists of 31 amino acids and is derived from proinsulin when it is converted into insulin. Recently, its various functions have been reported, including inhibition of leukocyte-endothelial interactions. We reported that attenuation of retinal ischemia-reperfusion injury was brought by inhibition of leukocyte-endothelial interactions in retinal microcirculation. We investigated whether retinal ischemia-reperfusion injury is attenuated by administration of C-peptide. Methods: Sixty minutes of retinal ischemia was induced by constriction of the optic nerve sheath of male Long Evans rats. The rats were divided into two groups; one group continuously treated with C-peptide immediately after reperfusion (IR-CP) and the other group treated with vehicle alone (IR). Acridine Orange Digital Fluorography was performed at 6, 12, 24 hours after reperfusion to evaluate leukocyte dynamics in retinal microcirculation in vivo. Vessel diameters were also measured. Results: In IR group, leukocyte rolling on venous endothelium peaked at 12 hours after reperfusion. Leukocyte accumulation in retina was the maximum over 12 hours and 24 hours after reperfusion. Major retinal veins dilated and reached the maximal diameters at 24 hours after reperfusion, whereas major retinal arteries showed no significant changes. All of those changes, i.e. leukocyte rolling, leukocyte accumulation and venous dilatation, were significantly attenuated in IR-CP group. Conclusions: C-peptide attenuated the retinal leukocyte-endothelial interactions in retinal ischemia-reperfusion model. It is suggested that the subsequent tissue injury could also be attenuated by C-peptide administration.

Keywords: ischemia • inflammation • cell adhesions/cell junctions