A RHO kinase inhibitor, AMA0526 improves corneal wound healing after alkali burn injury

Abstract

AbstractPurpose The aim of this study was to investigate the efficacy of a locally active ROCK‐inhibitor AMA0526 (Amakem NV) on corneal wound healing induced by alkali burn in an in vivo mouse model.Methods Swiss mice were divided randomly into 3 groups after chemical cauterization of the cornea by alkali. Topical treatment was initiated after the injury and given once daily. All groups received 0.1% of the active ROCK‐inhibitor AMA0526 topical in one eye and vehicle, bevacizumab (2.5%) or dexamethasone (0.1%) in the contralateral eye. A forth group received no treatment and was used as control. Corneal opacity and corneal neovascularization were graded every other day according to a 0‐4 scoring. Blood vessel formation and corneal leukocytes infiltration after injury were assessed by immunohistochemistry.Results Both corneal opacity and neovascularization were reduced after AMA0526 treatment compared to the vehicle treated eye. Infiltration of inflammatory cells and blood vessel formation were significantly inhibited at day 7. AMA0526 treated mice showed significant reduced corneal opacity and inflammation compared to mice treated with bevacizumab. AMA0526 proved to be as efficient as dexamethasone in reducing excessive corneal wound healing.Conclusion Targeting ROCK with a local ROCK inhibitor, AMA0526 is efficacious in improving and preventing corneal opacity and neovascularization after alkali burn. The results presented indicate that ROCK is an appealing target to treat and prevent corneal scarring and neovascularization and illustrate the potential therapeutic benefits of the local ROCK inhibitor, AMA0526.