THE PREVENTION OF DIABETIC RETINAL AND RENAL BASEMENT-MEMBRANE THICKENING IN MICE BY ISLET CELL ALLOGRAFTS

The effect of fetal islet cell allografts on retinal capillary (RCBMT) and glomerular (GBMT) basement membrane thickening in diabetic mice was studied, as well as the effect of diabetes on the anterior lens capsule and the inner lamina of Descement's membrane. CBA mice rendered diabetic with streptozotocin received fetal pancreatic islet cell grafts from C3H and BALB/c donors four weeks after induction of diabetes with an additional late transplant group receiving C3H grafts after six months of diabetes. After 12 months animals with successful grafts were examined for RCBMT along with untreated diabetics (UD, n = 4) and normals (N, n = 9). Untreated diabetics had significantly increased RCBMT (167.1 ± 12.1 vs 129.2 ± 24.3 nm, p = 0.05) and GBMT (278 ± 11 vs 248 ± 6 nm, p = 0.004) compared to normals. All graft recipients had RCBMT similar to normal and significantly less than untreated diabetics: BALB/c (n = 7), 123.8 ± 21.0, p = 0.02; C3h early (n = 5), 126.6 ± 21.7, p = 0.05; C3H late (n = 4), 134.4 ± 16.9, p = 0.03. The same was true for GBMT; 250 ± 10 nm, p = 0.02 for BALB/c recipients, 250 ± 8 nm, p = 0.04 for early and 255 ± 9 nm, p = 0.02 for late C3H recipients. GMBT in six month biopsies of normals and prospective late graft recipients were well below these levels. The anterior lens capsule and inner lamina of Descemet's membrane were not thickened in diabetic mice compared to normals, suggesting that factors associated with proximity to the circulation, apart from hyperglycaemia, may also be important in the generation of basement membrane thickening. This study supports the notion that islet cell allografts should prevent the long-term retinal and renal complications of diabetes if performed early in the disease.