Contrast Enhanced MRI Studies of Blood Retinal Barrier Damage in the Diabetic Rat

Abstract

Abstract: : Purpose: To test the hypothesis that damage to the blood retinal barrier is an early event in the course of experimental diabetic retinopathy. Methods: Blood retinal barrier permeability surface product (PS, cm³/min) was measured in urethane anesthetized rats using dynamic contrast (Gd-DTPA) enhanced MRI (DCE-MRI) after either sodium iodate (30 mg/kg, ip) injection, vascular endothelial growth factor (0.5 µg VEGF/2 ul, intravitreally, 6 hr prior) or vehicle (2 µl, HSA) injection, or in 2 and 4 mo diabetic (and control) rats. PS values in all groups were adjusted for incoherent baseline noise as measured in the control animals. Results: In non-injected and HSA injected control rats, BRB PS was 0 + 0.2 x 10^-6 cm³/min (mean + SEM, n = 16). BRB PS in sodium iodate treated rats exhibiting BRB damage (17.8 + 2.7 x 10^-6 cm³/min, n = 7) was significantly different (P < 0.05) from the control PS. A linear relationship was found between average vitreous signal enhancement (E) and Gd-DTPA dose (E = -1.5 + 518 (GAD DOSE), r = 0.98, P << 0.05). In VEGF injected eyes, BRB PS value (5.0 + 1.5 x 10^-6 cm³/min, n = 5) was significantly different (P < 0.05) from the control PS (0 + 0.2 x 10^-6 cm³/min). BRB PS in 2 and 4 mo diabetic rats (-0.2 + 0.2 x 10^-6 cm³/min, n = 5 and -0.3 + 0.3 x 10^-6 cm³/min, n = 5, respectively) were not significantly different (P > 0.05) from controls (0 + 0.2 x 10^-6 cm³/min). Conclusions: DCE-MRI provides a non-invasive and precise quantitative measure of BRB PS in rats. These data do not support the hypothesis that damage to the BRB occurs early in the time course of diabetes in the rat.

Keywords: animal model • imaging methods (CT, FA, ICG, MRI, OCT, RTA, S • blood supply