Background and purpose
The kinin B1 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 B1 receptors in retina of streptozotocin diabetic rats. Experimental approach: The distribution of B1 receptors on retinal cell types was investigated by immunocytochemistry. Effects of B1 receptor agonist, R-838, and antagonist, R-954, on retinal leukocyte adhesion, gene expression of kinin and VEGF systems, B1 receptor immunoreactivity, microgliosis and capillary leakage were measured. Effect of B1 receptor siRNA on gene expression was also assessed. Key
Purpose
The kinin B1 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 B1 receptors in retina of streptozotocin diabetic rats. Experimental approach: The distribution of B1 receptors on retinal cell types was investigated by immunocytochemistry. Effects of B1 receptor agonist, R-838, and antagonist, R-954, on retinal leukocyte adhesion, gene expression of kinin and VEGF systems, B1 receptor immunoreactivity, microgliosis and capillary leakage were measured. Effect of B1 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. B1 receptor mRNA levels remained increased at 6 months. B1 receptor immunolabelling was detected in vascular layers of the retina, on glial and ganglion cells. Intravitreal R-838 amplified B1 and B2 receptor gene expression, B1 receptor levels (immunodetection), leukostasis and vascular permeability at 2 weeks in STZ-retina. Topical application (eye drops) of R-954 reversed these increases in B1 receptors, leukostasis and vascular permeability. Intravitreal B1 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.