| Autor: |
Bhat M; School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, Canada.; Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada., Shirzad S; School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, Canada., Fofana AK; School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, Canada., Gobeil F Jr; Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada., Couture R; Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada., Vaucher E; School of Optometry, Université de Montréal, Montreal, QC H3T 1P1, Canada. |
| Abstrakt: |
The kallikrein-kinin system (KKS) contributes to vascular inflammation and neovascularization in age-related macular degeneration (AMD), particularly via the kinin B 1 receptor (B 1 R). The aim of the present study was to determine the protective effects of the topical administration of the B 1 R antagonist (R-954) on inflammation, neovascularization, and retinal dysfunction in a murine model of neovascular AMD. Choroidal neovascularization (CNV) was induced in C57BL6 mice using an argon laser. A treatment with ocular drops of R-954 (100 μg/15 μL, twice daily in both eyes), or vehicle, was started immediately on day 0, for 7, 14, or 21 days. CNV, invasive microglia, and B 1 R immunoreactive glial cells, as well as electroretinography alterations, were observed within the retina and choroid of the CNV group but not in the control group. The staining of B 1 R was abolished by R-954 treatment as well as the proliferation of microglia. R-954 treatment prevented the CNV development (volume: 20 ± 2 vs. 152 ± 5 × 10 4 µm 3 in R-954 vs. saline treatment). R-954 also significantly decreased photoreceptor and bipolar cell dysfunction (a-wave amplitude: -47 ± 20 vs. -34 ± 14 µV and b-wave amplitude: 101 ± 27 vs. 64 ± 17 µV in R-954 vs. saline treatment, day 7) as well as angiogenesis tufts in the retina. These results suggest that self-administration of R-954 by eye-drop treatment could be a promising therapy in AMD to preserve retinal health and vision. |
