Abstract
Purpose: :
Pathological changes of the retinal microcirculation in diabetes are the result of oxidative stress and inflammatory mechanisms induced by hyperglycaemia. Recent studies suggest that the inducible kinin B1 receptor (B1R) is overexpressed in retinal microvessels of Streptozotocin-diabetic rats. The activation of B1R dilates retinal microvessels in a perfused isolated retinal preparation. Moreover, B1R enhances vascular permeability in this model, a pathologic feature of diabetic retinopathy.Objective: To determine whether B1R could contribute to the early retinal blood flow changes occurring in type 1 diabetes.
Methods: :
Male Wistar rats weighting 200-225g were made diabetic with a single i.p. injection of Streptozotocin (STZ, 65 mg/kg). Age-matched controls received sodium citrate buffer vehicle. On the fourth day post-STZ injection, the B1R antagonist SSR240612 was administrated orally (10 mg/kg) 3 hours prior to retinal blood flow measurement. Retinal perfusion was measured in awake animals by autoradiography using N-isopropyl-p-14C-iodoamphetamine (14C-IMP, 100 µCi/kg, i.v. injection) as a tracer. The rats were sacrificed two minutes after IMP injection, the eyes were enucleated and both retinas were dissected out. One retina was digested and the amount of total radioactivity was determined with a scintillation counter. The other retina was whole-mounted on a glass slide and exposed on X-ray film for the evaluation of regional changes.
Results: :
Blood flow was not significantly altered in STZ-diabetic rats (80 ± 16 ml/100g/min) 4 days after diabetes onset compared to control rats (91 ± 23 ml/100g/min) (P=0.8). Moreover, the treatment with SSR240612 did not significantly alter retinal blood flow in STZ-diabetic rats (77 ± 17 ml/100g/min) (P=0.76).
Conclusions: :
The up-regulated B1R in the diabetic retina does not affect blood flow in the early stage of diabetes. Thus the blood-retinal breakdown previously described in this model at this time is unlikely attributed to an increase of capillary perfusion pressure.
Keywords: retina • diabetes • blood supply