ISLET TRANSPLANTATION INHIBITS DIABETIC-RETINOPATHY IN THE SUCROSE-FED DIABETIC COHEN RAT

Purpose. To study the effect of islet transplantation on the developme nt of diabetic retinopathy in the sucrose-fed diabetic Cohen rat, a us eful experimental model of accelerated microvascular disease. Methods. Syngeneic transplantation of collagenase-ficoll isolated islets by in traportal injection was performed either after 6 weeks or after 12 wee ks of diabetes, i.e., before or after the first morphologic retinal ch anges, respectively. Retinal digest preparations were examined using q uantitative morphologic parameters. Results. After 26 weeks of diabete s, characteristic features of background retinopathy such as a 5% incr ease in capillary endothelial cells, a 27% pericyte dropout, acellular occluded vessels and, occasionally, microaneurysms developed in untre ated animals. Islet transplantation performed after 6 weeks of diabete s completely prevented endothelial cell proliferation and diminished p ericyte loss (2950 +/- 140 vs 2390 +/- 40 in diabetic controls, P < 0. 01). A significant increase in acellular occluded capillaries persiste d (31 +/- 14 vs 8 +/- 2 in NC; P < 0.01). Islet transplantation after 12 weeks of diabetes, i.e., after established pericyte loss, only part ially restored capillary cell composition and did not prevent retinal vessel occlusion. These findings indicate that the beneficial effect o f islet transplantation on diabetic retinopathy is limited to a time v ery early in the evolution of this process. Conclusions. These data su ggest that irreversible changes induced by antecedent hyperglycemia pl ay a central role in the progressive development of diabetic retinopat hy.