Abstract
PurposeKinin B1 receptor (B1R) is upregulated in retina of Streptozotocin (STZ)-diabetic rats and contributes to vasodilation of retinal microvessels and breakdown of the blood-retinal barrier. Systemic treatment with B1R antagonists reversed the increased retinal plasma extravasation in STZ rats. The present study aims at determining whether ocular application of a water soluble B1R antagonist could reverse diabetes-induced retinal inflammation and oxidative stress.MethodsWistar rats were made diabetic with STZ (65 mg/kg, i.p.) and 7 days later, they received one eye drop application of LF22-0542 (1% in saline) twice a day for a 7 day-period. The impact was determined on retinal vascular permeability (Evans blue exudation), leukostasis (leukocyte infiltration using Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin), retinal mRNA levels (by qRT-PCR) of inflammatory (B1R, iNOS, COX-2, ICAM-1, VEGF-A, VEGF receptor type 2, IL-1β and HIF-1α) and anti-inflammatory (B2R, eNOS) markers and retinal level of superoxide anion (dihydroethidium staining).ResultsRetinal plasma extravasation, leukostasis and mRNA levels of B1R, iNOS, COX-2, VEGF receptor type 2, IL-1β and HIF-1α were significantly increased in diabetic retinae compared to control rats. All these abnormalities were reversed to control values in diabetic rats treated with LF22-0542. B1R antagonist also significantly inhibited the increased production of superoxide anion in diabetic retinae.ConclusionB1R displays a pathological role in the early stage of diabetes by increasing oxidative stress and pro-inflammatory mediators involved in retinal vascular alterations. Hence, topical application of kinin B1R antagonist appears a highly promising novel approach for the treatment of diabetic retinopathy.
Highlights
Recent findings suggest a role for the kallikrein-kinin system in the development of diabetic retinopathy [1,2,3]
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The present study aims at determining whether topical ocular application of LF22-0542, a non-peptide water soluble B1 receptor (B1R) antagonist, could reverse diabetes-induced retinal inflammation and oxidative stress
Summary
Recent findings suggest a role for the kallikrein-kinin system in the development of diabetic retinopathy [1,2,3]. Kinins are important inflammatory mediators involved in tissue edema, leukocytes infiltration, vasodilation and regulation of local blood flow [4]. These peptides are produced at the site of inflammation and exert their effects through the activation of two G-proteincoupled receptors named B1 (B1R) and B2 (B2R) [5,6]. B1R is expressed at very low levels in physiological conditions. This inducible receptor is upregulated in response to tissue injury, by proinflammatory cytokines or by the oxidative stress associated to hyperglycemia.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
