THE EFFECT OF LOCAL ROCK-INHIBITION ON CORNEAL SCARRING AFTER ALKALI BURN INJURY

Abstract

Purpose: The aim of this study was to investigate the efficacy of a local ROCK-inhibitor AMA0526 (Amakem NV) on corneal scarring induced by alkali burn in an in vivo mouse model.

Methods: Male Swiss mice (aged 6-8 weeks) 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. The first group received 0.1% of the local ROCK-inhibitor AMA0526 versus Vehicle (experimental group 1), the second group was treated with bevacizumab (Avastin; anti-VEGF) versus AMA0526 (experimental group 2) and the third group was used as control and received no treatment. Corneal opacity and corneal neovascularization were graded every other day according to a 0-4 scoring. Blood vessel formation, collagen deposition and macrophage corneal infiltration after injury were assessed and compared by immunohistochemistry on day 7 and 14 after alkali burn.

Results: Both corneal opacity and neovascularization were reduced after AMA0526 treatment compared to the vehicle treated eye (p<0.05 at day 5, 7 and 9). Infiltration of inflammatory cells (p=0.000056; 22.27% reduction) and blood vessel formation (p=0.00208; 42.26% reduction) were significantly inhibited at day 7. No clear reduction of fibrosis was seen. No significant differences could be observed in corneal neovascularization and immunohistological analyses in the experimental group 2. However, AMA0526 treated mice showed significant reduced corneal opacity compared to mice treated with bevacizumab.

Conclusions: 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.

Keywords: 480 cornea: basic science • 765 wound healing • 609 neovascularization