NORMALIZATION OF RETINAL BLOOD-FLOW IN DIABETIC RATS WITH PRIMARY INTERVENTION USING INSULIN PUMPS

Purpose. Prior results have demonstrated a significant reduction in re tinal blood flow in streptozotocin (STZ)-induced diabetic rats. These studies were extended to investigate whether retinal blood flow change s, in the diabetic rat model, could be prevented with strict glycemic control using insulin pumps. Retinal blood flow changes also were meas ured during hyperoxia and after intravitreal histamine infusion to val idate the methodology. Methods. Retinal blood flow changes were measur ed using video-based fluorescein angiography and computer-assisted ima ge analysis. A total of 48 male Sprague-Dawley and 9 Brown Norway rats were used in these experiments. Retinal blood flow after primary insu lin intervention was evaluated in diabetic rats implanted with miniosm otic insulin pumps within 24 hours of STZ-induced diabetes. Diabetic r ats, not treated with insulin, were used for comparison. Results. Hype roxia caused a significant (P = 0.001) reduction (54%) in retinal bloo d flow, whereas intravitreal infusion of 10(-3) M histamine caused a s ignificant (P = 0.009) increase (108%) in retinal blood flow. Retinal blood flow in the primary insulin intervention group, after 1 week of diabetes, was not statistically different from retinal blood flow of n ondiabetic controls as measured at baseline from the animals used in t he hyperoxia and histamine infusion experiments. In contrast there was a significant (P = 0.0001) retinal blood flow reduction in the untrea ted diabetic group. Conclusions. The results showed that the local eff ect of histamine and hyperoxia on the retina produced the expected res ponses in retinal blood flow, further confirming the validity of the m ethodology. Primary insulin intervention demonstrated that strict glyc emic control initiated immediately after induction of diabetes was suf ficient to maintain normal retinal blood flow in STZ-induced diabetic rats.