Expression, distribution and function of kinin
receptor in the rat diabetic retina
Elvire Vaucher, École d’optométrie, Université de Montréal, C.P.6128, Succursale Centre Ville, Montréal, QC H3C 3J7,
Canada. E-mail: email@example.com
28 June 2017;
22 November 2017;
15 December 2017
, Jacques Sénécal
, Frédéric Huppé-Gourgues
, Réjean Couture
École d’optométrie, Université de Montréal, Montréal, QC, Canada, and
Département de Pharmacologie et Physiologie, Université de Montréal,
Montréal, QC, Canada
The two senior authors contributed equally to the work.
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.
The distribution of B
receptors on retinal cell types was investigated by immunocytochemistry. Effects of B
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.
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
immunolabelling was detected in vascular layers of the retina, on glial and ganglion cells. Intravitreal R-838 ampliﬁed 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
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.
BK, bradykinin; DR, diabetic retinopathy; GCL, ganglion cell layer; GFAP, glial ﬁbrillary acid protein; Iba-1, ionized
calcium-binding adapter molecule 1; INL, inner nuclear layer; IPL, inner plexiform layer; ONL, outer nuclear layer; qRT-
PCR, real-time quantitative RT-PCR; R-838, Sar-[D-Phe
-BK; R-954, AcOrn [Oic
BK; RECA-1, rat endothelial cell antigen-1; STZ, streptozotocin
British Journal of
British Journal of Pharmacology (2018) 175 968–983 968
DOI:10.1111/bph.14138 © 2017 The British Pharmacological Society