Abstract
Purpose :
Runt-related transcription factor 1 (RUNX1) inhibition is a novel therapeutic strategy in ocular neovascularization and has previously been shown to be safe and effective for the treatment of retinal and choroidal neovascularization in animal models. Furthermore, topical application of RUNX1 inhibitor, Ro5-3335, as a nanoemulsion (eNano-Ro5) has demonstrated efficacy in experimental proliferative vitreoretinopathy. This study assessed the preclinical efficacy of topical RUNX1 inhibition in alkali burn-induced corneal neovascularization
Methods :
6-8-week-old C57BL/6J male and female mice were used for this study. eNano-Ro5 was administered topically four times a day after alkali burn-induced corneal neovascularization. To induce the corneal injury, a 2-mm paper disc soaked in 1M NaOH was placed on the surface of the central cornea for 30 seconds followed by a thorough washing with saline solution for 60 seconds. Animals were evaluated with slit lamp examination at days 1, 3, 7 and 14. Corneal defect, corneal opacity and corneal neovascularization were analyzed after treatment with either eNano-Ro5 (n=22) or vehicle (n=23) for 14 days after alkali burn. We also included another group treated with Dexamethasone 0.1% (n=9)
Results :
RUNX1 positive cells were observed after injury by immunofluorescence within the corneal tissue. We found a significant reduction in corneal defect in the eNano-Ro5 treated group compared to control at day 14 (P<0.05). In addition, corneal opacity was significantly improved at day 1, 7 and 14 in the eNano-Ro5 treated animals (P<0.05, P<0.05 and P<0.01, respectively). Corneal neovascularization was also significantly reduced at day 14 compared to control (P<0.01). In the dexamethasone group, we found persistent corneal defect (P<0.001), improved corneal transparency at day 3, 7 and 14 (P<0.001, P<0.01 and P<0.001) and reduced neovascularization at day 7 and 14 (P<0.05 and P<0.001)
Conclusions :
The severe reduction in corneal thickness observed in the dexamethasone-treated group may explain the reduced corneal opacity and neovascularization. Taken together, these findings suggest a beneficial effect of RUNX1 inhibition with topical eNano-Ro5 in preventing the blinding effects of alkali burn injury. This could be a potential therapy to treat this sight-threating condition
This is a 2021 ARVO Annual Meeting abstract.