VITREAL INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBPS) ARE INCREASED IN HUMAN AND ANIMAL DIABETICS

Although patients with diabetic retinopathy have been reported to have elevated vitreal IGF-I levels, it is not known whether diabetes also affects the levels of vitreal IGF binding proteins (IGFBPs) which cont rol IGF's bioavailability. To address this issue, vitreal IGFBP levels were assayed in human diabetics, rats with streptozotocin-induced dia betes and galactose-fed dogs with diabetic-like retinopathy. Using I-1 25-IGF-II ligand blots, it was found that human diabetics have a 4-fol d increase in vitreal IGFBP levels. Also, western blots on human diabe tic vitreous reveal increased levels of IGFBP-2 and proteolytic fragme nts of IGFBP-3. IGF binding assays on vitreous from streptozotocin-tre ated rats (three months in duration) also indicate a 5-fold increase i n IGF binding activity. IGF ligand blots using vitreous from rats with a shorter duration of diabetes (one month) show a 63% increase in IGF BP binding and a marked decrease in serum IGFBP binding. IGF ligand bl ots and IGFBP-2 and -4 western blots using vitreous from galactose-fed dogs with diabetic-like retinopathy exhibit a 6-fold increase in vitr eal IGFBPs. The observation that vitreal IGFBPs are elevated in diabet ic humans and rats without overt retinopathy suggests that these incre ases are not the result of a preexisting end-stage retinopathy but rat her are an early ocular event in the diabetic process. Increases in vi treal IGFBPs thus could participate in the proliferative aspects of di abetic retinopathy by virtue of their putative intrinsic bioactivity o r their capacity to alter IGF bioavailability.