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Abstract
Damage to the corneal epithelium can be caused by microbial, chemical, or physical insults, and delayed wound healing can leave the underlying stroma vulnerable to infection and ulceration which may result in vision loss. Alkali injuries are some of the most severe ocular injuries and cause acute inflammation, which is characterised by rapid infiltration of PMNs into cornea. Corneal alkali injuries can have many complications which can interfere with the healing of the cornea and can result in the non-healing corneal defects, scarring and chronic inflammation. Therefore it is critical to repair corneal epithelial damage as rapidly as possible to maintain corneal epithelial integrity.
Lactoferrin is present in tears (~2 mg/ml) and has anti-microbial and anti-inflammatory properties. Since lactoferrin is effective in treating wounds elsewhere in the body, it may also play a role in promoting corneal epithelial wound healing. The aim of the study was to investigate the role of bovine lactoferrin (BLF) in alkali-induced corneal epithelial wound healing in-vitro, to understand the mechanism of action of BLF in promoting in vitro wound healing and to explore its potential as a therapeutic agent for treating corneal alkali injury in an animal model.
It was demonstrated that BLF accelerates healing of alkali-induced wounds in both in vitro and in vivo. BLF at concentration ≥ 2.5 mg/ml promotes in vitro healing of alkali-induced wound through up-regulation of IL-6 and PDGF-BB. Further studies have demonstrated that BLF promotes wound healing through interaction with the cell surface receptor LRP and up-regulates IL-6 and PDGF through p38MAPK, JNK and ERK1/2 signal transduction pathways. BLF accelerated healing of alkali injury in vivo which is consistent with the in vitro findings. However, the mechanism by which BLF stimulates wound healing in vivo involves reducing inflammation via a reduction in IL-1 rather than through IL-6 and PDGF upregulation as proposed in the in vitro studies. These results indicate that the administration of BLF may have a clinical application in the treatment of alkali injury in reducing inflammation and promoting healing of corneal epithelial defects.