Blockade of diabetes-induced increase in retinal vascular permeability and MMP9 activity in uPAR-/- mice.

<p>Diabetic and non-diabetic uPAR-/- mice and their congenic controls (uPAR+/+, uPAR+/-) were injected intravenously with Alexa-Fluor 488-BSA (10 mg/kg) and permeability was quantified as described in the methods section. Permeability was significantly increased in the diabetic uPAR+/+ or uPAR+/- mice compared with the non-diabetic controls (A). Permeability was not increased in the uPAR-/- mice. n=4-6. C, control; D, diabetic; *, <i>P</i><0.01 <i>versus</i> non-diabetic control; #, <i>P</i><0.01 <i>versus</i> uPAR+/+ and uPAR+/- diabetic. Gelatin zymograms prepared using vitreous samples collected from the same mice showed prominent increases in MMP9 activity in the uPAR+/+ and uPAR+/- diabetic mice. MMP9 activity was absent in retinas from uPAR-/- diabetic mice and non-diabetic controls (B). Retinal sections from diabetic and control mice were immunolabeled with anti-phospho-GSK3β antibody (green) and Texas red-isolectin B4 (red) (C). This analysis showed that phospho-GSK3β co-localizes with the lectin-positive vessels in the diabetic retina (arrows) and is present in microglial-like cells (arrowheads) in both control and diabetic retinas.