Abstract
Purpose: :
Recent studies proposed that kinin B1 receptor (B1R) is involved in retinal vascular damage in diabetic rats, i.e. changes in vasoreactivity and breakdown of the blood-retinal barrier. B1R is upregulated in retina of Streptozotocin (STZ)-diabetic rats by oxidative stress, suggesting that treatment with B1R antagonists could improve retina homeostatis in diabetes. The present study aims at determining whether topical administration of a B1R antagonist, FV-60135-02, could reverse retinal vascular hyperpermeability, leukostasis and inflammatory mediators putatively involved in diabetic retinopathy.
Methods: :
Wistar rats were rendered diabetic by a single injection of STZ (65 mg/kg, i.p.). 7 days later, rats were treated twice a day with one eye drop application of FV-60135-02 (1% in saline) for a 7 day-period. On the last day of treatment, retinal vascular permeability, leukostasis and retinal mRNA levels of B1R, B2R, iNOS, eNOS, COX-2, ICAM-1, VEGFα, VEGF receptor type 2, IL-1β and HIF-1α were measured by quantitative RT-PCR.
Results: :
Retinal plasma extravasation (Evans Blue/g wet tissue, n = 9-11) was significantly increased in STZ-diabetic rats (25.7 ± 1.9 µg) compared to control rats (19.6 ± 1.1 µg) and blocked by FV-60135-02 (19.9 ± 1.6 µg). Number of adherent leukocytes in retinal vessels was significantly increased in diabetic rats (164 ± 27, n = 5) compared to control rats (106 ± 38, n = 7) and decreased in diabetic rats treated with FV-60135-02 (111 ± 43, n = 7). mRNA levels of B1R, iNOS, COX-2, VEGF receptor type 2, IL-1β and HIF-1α were significantly increased in diabetic retinas compared to control rats and were back to control values by FV-60135-02.
Conclusions: :
Topical application of kinin B1R antagonist is found as an effective and non-toxic approach to reverse increased vascular permeability and leukostasis in diabetes. B1R seems to have a pathological role in the early stage of diabetes by interacting with other factors involved in inflammation and retinal vascular damage.
Keywords: diabetic retinopathy • inflammation