FIGURE 2.

Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) attenuates retinal inflammation and prevents diabetes-induced blood-retinal barrier (BRB) breakdown. The BRB breakdown [panel (A)] was quantified with the fluorescein isothiocyanate-conjugated dextran technique after treatment with intravitreal injection of 350 μM TIMP-3 in 5 μl in one eye and the same volume of phosphate-buffered saline (PBS) in the contralateral eye of rats 10 weeks after induction of diabetes. Results are expressed as mean ± standard deviation of five rats in each group. Evaluation of inflammatory mediators was evaluated shortly after diabetes induction (see section “Materials and Methods”). Western blot analysis of rat retinas was performed to evaluate protein expression levels of phospho-ERK1/2 [panel (B)], the p65 subunit of NF-κB [panel (C)], intercellular adhesion molecule-1 (ICAM-1) [panel (D)], and vascular endothelial growth factor (VEGF) [panel (E)]. Results are expressed as mean ± standard deviation of 12 rats in each group. One-way ANOVA and independent t-test were used for comparisons between the three and two groups, respectively, panels (A–E). *p < 0.05 compared with non-diabetic controls. ^#p < 0.05 compared with PBS-treated diabetic rats.