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Expression, distribution and function of kinin B 1 receptor in the rat diabetic retina
Author(s) -
Hachana Soumaya,
Bhat Menakshi,
Sénécal Jacques,
HuppéGourgues Frédéric,
Couture Réjean,
Vaucher Elvire
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14138
Subject(s) - leukostasis , retina , kinin , receptor , endocrinology , medicine , biology , receptor expression , diabetic retinopathy , retinal , vascular permeability , bradykinin , diabetes mellitus , neuroscience , biochemistry
Background and Purpose The kinin B 1 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 1 receptors in retina of streptozotocin diabetic rats. Experimental Approach The distribution of B 1 receptors on retinal cell types was investigated by immunocytochemistry. Effects of B 1 receptor agonist, R‐838, and antagonist, R‐954, on retinal leukocyte adhesion, gene expression of kinin and VEGF systems, B 1 receptor immunoreactivity, microgliosis and capillary leakage were measured. Effect of B 1 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 1 receptor mRNA levels remained increased at 6 months. B 1 receptor immunolabelling was detected in vascular layers of the retina, on glial and ganglion cells. Intravitreal R‐838 amplified B 1 and B 2 receptor gene expression, B 1 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 1 receptors, leukostasis and vascular permeability. Intravitreal B 1 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 1 receptors on endothelial and glial cells in acute and advanced phases of DR. Topical application of the B 1 receptor antagonist R‐954 seems a feasible therapeutic approach for the treatment of DR.