Expression, distribution and function of kinin B receptor in the rat diabetic retina.

BACKGROUND AND PURPOSE

The kinin B receptor contributes to vascular inflammation and blood-retinal barrier breakdown in diabetic retinopathy (DR). We investigated the changes in expression, cellular localization and vascular inflammatory effect of B receptors in retina of streptozotocin diabetic rats.

EXPERIMENTAL APPROACH

The distribution of B receptors on retinal cell types was investigated by immunocytochemistry. Effects of B receptor agonist, R-838, and antagonist, R-954, on retinal leukocyte adhesion, gene expression of kinin and VEGF systems, B receptor immunoreactivity, microgliosis and capillary leakage were measured. Effect of B receptor siRNA on gene expression was also assessed.

KEY RESULTS

mRNA levels of the kinin and VEGF systems were significantly enhanced at 2 weeks in streptozotocin (STZ)-retina compared to control-retina and were further increased at 6 weeks. B receptor mRNA levels remained increased at 6 months. B receptor immunolabelling was detected in vascular layers of the retina, on glial and ganglion cells. Intravitreal R-838 amplified B and B receptor gene expression, B receptor levels (immunodetection), leukostasis and vascular permeability at 2 weeks in STZ-retina. Topical application (eye drops) of R-954 reversed these increases in B receptors, leukostasis and vascular permeability. Intravitreal B receptor siRNA inhibited gene expression of kinin and VEGF systems in STZ-retina. Microgliosis was unaffected by R-838 or R-954 in STZ-retina.

CONCLUSION AND IMPLICATIONS

Our results support the detrimental role of B receptors on endothelial and glial cells in acute and advanced phases of DR. Topical application of the B receptor antagonist R-954 seems a feasible therapeutic approach for the treatment of DR.