Normalization of retinal blood flow in diabetic rats with primary intervention using insulin pumps.
OBJECTIVE
Prior results have demonstrated a significant reduction in retinal blood flow in streptozotocin (STZ)-induced diabetic rats. These studies were extended to investigate whether retinal blood flow changes, in the diabetic rat model, could be prevented with strict glycemic control using insulin pumps. Retinal blood flow changes also were measured during hyperoxia and after intravitreal histamine infusion to validate the methodology.


METHODS
Retinal blood flow changes were measured using video-based fluorescein angiography and computer-assisted image analysis. A total of 48 male Sprague-Dawley and 9 Brown Norway rats were used in these experiments. Retinal blood flow after primary insulin intervention was evaluated in diabetic rats implanted with mini-osmotic insulin pumps within 24 hours of STZ-induced diabetes. Diabetic rats, not treated with insulin, were used for comparison.


RESULTS
Hyperoxia caused a significant (P = 0.001) reduction (54%) in retinal blood flow, whereas intravitreal infusion of 10(-3) M histamine caused a significant (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 nondiabetic controls as measured at baseline from the animals used in the hyperoxia and histamine infusion experiments. In contrast there was a significant (P = 0.0001) retinal blood flow reduction in the untreated diabetic group.


CONCLUSIONS
The results showed that the local effect of histamine and hyperoxia on the retina produced the expected responses in retinal blood flow, further confirming the validity of the methodology. Primary insulin intervention demonstrated that strict glycemic control initiated immediately after induction of diabetes was sufficient to maintain normal retinal blood flow in STZ-induced diabetic rats.
Clermont
A C
AC
Beetham Eye Institute, Joslin Diabetes Center, Boston, MA 02215.
Brittis
M
M
Shiba
T
T
McGovern
T
T
King
G L
GL
Bursell
S E
SE
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D005451:Fluorescein Angiography; D007091:Image Processing, Computer-Assisted / Q000379:methods; D015918:Infusion Pumps, Implantable; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000503:physiopathology*; D013311:Streptozocin
D007328:Insulin; D013311:Streptozocin