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K. A. Patil, L. Bellner, S. Lokhande, M. W. Dunn, N. G. Abraham, M. Laniado Schwartzman; Carbon Monoxide Donor Enhances Corneal Re-Epithelialization in Heme Oxygenase (HO)-2 Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2380. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
HO represents an intrinsic cytoprotective and anti-inflammatory system based on its ability to modulate leukocyte migration and to inhibit expression of inflammatory cytokines and proteins via its products biliverdin/bilirubin and carbon monoxide (CO). Lack of HO activity results in unresolved corneal inflammation and chronic inflammatory complications including ulceration, perforation and neovascularization. This study was undertaken to investigate the effects of CORM-3, a water-soluble CO-releasing agent on inflammation and wound healing in a model of epithelial injury in HO-2 null mice.
HO-2 null mice (HO-2 -/-) were treated with CORM-3 (15mg/kg, ip; plus topical (10 µl of 0.075mg /100ul) or its vehicle (Hank’s balanced salt solution, pH 7.4) one hour prior to injury and once daily. The corneal epithelium was removed using Alger Brush in anesthetized mice. Re-epithelialization was monitored by Fluorescein staining and quantified by image analysis with the Axiovision software (Zeiss). Corneas were dissected and processed for measurements of mRNA and cytokines. All the animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
CORM-3 treatment accelerated re-epithelialization when compared with vehicle-treated group by 15%, 20% and 25% at days 2, 4 and 7 after injury, in HO-2 -/- mice respectively (n=8, p<0.05). Corneal neovascularization that constantly follows epithelial injury in HO-2 -/- mice was also reduced in the CORM-3 treated animals by 50-60% when compared with the vehicle treated group. These effects were associated with reduction in the levels of inflammatory chemokines including MCP-1 and MIP-2 and with a reduction in the levels of VEGF mRNA.
HO-2 null mice display decreased HO activity exemplified by reduced production of CO which has been shown to exert anti-inflammatory and cytoprotective properties. Indeed, supplementation of CO via administration of CORM-3 rescues aberrant reparative response to injury in the HO-2 null mice corneas and significantly attenuated the exaggerated inflammation further enforcing the importance of the HO system, the primary source fro endogenous CO.
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