Islet transplantation inhibits diabetic retinopathy in the sucrose-fed diabetic Cohen rat.

Abstract

PURPOSE: To study the effect of islet transplantation on the development of diabetic retinopathy in the sucrose-fed diabetic Cohen rat, a useful experimental model of accelerated microvascular disease. METHODS: Syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection was performed either after 6 weeks or after 12 weeks of diabetes, i.e., before or after the first morphologic retinal changes, respectively. Retinal digest preparations were examined using quantitative morphologic parameters. RESULTS: After 26 weeks of diabetes, characteristic features of background retinopathy such as a 5% increase in capillary endothelial cells, a 27% pericyte dropout, acellular occluded vessels and, occasionally, microaneurysms developed in untreated animals. Islet transplantation performed after 6 weeks of diabetes completely prevented endothelial cell proliferation and diminished pericyte loss (2950 +/- 140 vs 2390 +/- 40 in diabetic controls, P < 0.01). A significant increase in acellular occluded capillaries persisted (31 +/- 14 vs 8 +/- 2 in NC; P < 0.01). Islet transplantation after 12 weeks of diabetes, i.e., after established pericyte loss, only partially restored capillary cell composition and did not prevent retinal vessel occlusion. These findings indicate that the beneficial effect of islet transplantation on diabetic retinopathy is limited to a time very early in the evolution of this process. CONCLUSIONS: These data suggest that irreversible changes induced by antecedent hyperglycemia play a central role in the progressive development of diabetic retinopathy.