Macrophage Dysfunction and Impaired Wound Healing in Corneas of Heme Oxygenase (HO)‐2 Deficient Mice

Abstract

Corneal epithelial injury in HO‐2 null (KO) mice leads to delayed wound healing, exaggerated inflammatory cell infiltration, unresolved inflammation, ulceration, perforation and neovascularization. We examined the effect of systemic macrophage (MØ) depletion, using clodronate liposomes, on corneal wound healing in WT and KO mice. The corneal epithelium was removed in control and MØ‐depleted WT and KO mice. MØ depletion of WT mice delayed corneal wound healing when compared with the control group by 15% at day 4 after injury (p<0.05). Surprisingly, MØ depletion of KO mice had no additional effect on an already impaired corneal wound healing. Furthermore, MØ depletion caused a 100% (p<0.05) increase in the number of PMNs in the corneas of WT mice, whereas no significant change in the number of accumulating PMNs was observed in the corneas of KO mice. HO‐2 silencing of RAW 264.7 MØ using HO‐2 shRNA reduced phagocytic capacity by 40% (p<0.05), whereas HO‐induction using SnCl2 increased phagocytic capacity by 85% (p<0.05). Together these data indicate that HO‐2 deletion impairs MØ function and that an intact HO‐2 is required for ordered inflammatory and repair response.Supported in part by NIH grant EY06513 (MLS).