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Dimitrios Karamichos, Pouriska Kivanany, Tina B McKay, Matthew Petroll; Quercetin inhibits corneal scar formation in vivo. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal scarring is a major cause of blindness around the world. Currently, there are no effective therapies for the treatment or prevention of corneal scarring following injury or infection. We have previously reported identification of a novel flavonoid, Quercetin, as a significant inhibitor of corneal fibrosis in vitro. Our current study tests the efficacy of Quercetin on corneal scarring in both mice and rabbit models.
Mice: Wild-type C57BL/6J mice aged 8-12 weeks were anesthetized with ketamine/xylazine injected intraperitoneal, and stromal scars were generated by epithelial and stromal debridement of 2x2mm using an Alger brush. Topical application of Quercetin at concentrations of 50, 5, 1, and 0.5mM or vehicle was administered following injury. Corneal scarring was assessed on day 21 using western blot and H&E. Rabbits: Six New Zealand White rabbits underwent lamellar keratectomy (LK) surgery, followed by treatment with either Quercetin (5 mM, 3 rabbits) or vehicle (3 rabbits) twice daily for three days (1 drop per dose). Stromal backscattering (haze) was assessed from 7 to 21 days using in vivo confocal microscopy.
Mice: A single dose of 5mM Quercetin significantly reduced scar formation compared to vehicle treated controls. Slight scar formation was observed at lower Quercetin levels (0.5mM and 1mM) but still significantly less when compared to controls. Quercetin treatment significantly reduced expression of fibrotic markers, α-smooth muscle actin and Collagen III. Rabbits: At 21 days after LK, stromal backscattering in control and Quercetin treated rabbits was 13,577 + 935 and 8501 + 3415 haze units, respectively (P value for two-tailed t-test = 0.068, Power = 0.472). No adverse effects of topical application of Quercetin were observed on mice or rabbits.
Topical application of a single low dose of Quercetin ameliorates stromal scar development in vivo. These results suggest that Quercetin may be a potent therapeutic for inhibiting fibrosis in the cornea. Further preclinical studies are needed to optimize drug dose and verify safety profile.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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