|Institution:||University of New South Wales|
|Department:||Optometry & Vision Science|
|Keywords:||Cornea; Lactoferrin; Healing; N-lobe; Glycosylation; Disulfide bonds; Guinea pig; Rabbit; Protease; Lactoferricin; Interleukin 6; Platelet derived growth factor; PDGF; IL-6; C-lobe; Iron; Glycoprotein; Denatured; Nutraceutical; Drug; Milk; Eye; Therapeutic; Debridement; Alkali burn; Proliferation; Migration; Epithelial; Histology; HCLE|
|Full text PDF:||http://handle.unsw.edu.au/1959.4/53574|
Background. Corneal abrasions are a common eye injury. Fortunately they typically resolve quickly and without consequence. However until they heal they remain painful and if healing is delayed infection and scaring that may permanently impair vision is possible. The number one eye injury causing delayed healing is the alkali burn, usually from a household cleaning product or workplace accident. There are currently no medications proven to accelerate re-epithelialisation of these wounds. Purpose. Isolate the region of bovine lactoferrin (BLF) that promotes corneal epithelial wound healing, determine the mechanism and assess its efficacy. Methods. An alkali burn was applied in vitro to human corneal epithelial cells that were then incubated with BLF fragments or structural variants while wound closure was monitored. The mechanism promoting healing was determined using assays for migration, proliferation and measuring interleukin-6 and platelet-derived-growth-factor-BB (PDGF) levels. Efficacy of the regions identified in vitro were tested in vivo using Guinea pig and rabbit models of debridement and alkali burn wounds treated with BLF, fragments of BLF, or the vehicle. Wound size was monitored. Results. The C-lobe of BLF promoted greater wound healing in vitro than equimolar BLF (P<0.05) or the N-lobe (P<0.001). Further fragmentation or significant disruption to the conformation of BLF resulted in no promotion of healing compared to the control. C-lobe promoted healing was associated with corneal epithelial up-regulation of PDGF and IL-6 over the control (P<0.001), increased cell migration rates compared to BLF (P<0.05) and a small increase in proliferation rates (P<0.05) over the control. In vivo the C-lobe accelerated early wound healing in the rabbit model. For Guinea pigs with debridement wounds by 24 hours complete re-epithelialisation was observed in 67% treated with C lobe (P=0.03) and 22% with BLF (P=0.67) compared to 0% for vehicle. In the Guinea pig alkali burn model C-lobe (P=0.007) and BLF (P=0.001) promoted faster closure than the vehicle but were not significantly different from each other. Conclusions. The C-lobe of BLF promotes corneal epithelial wound healing. For abrasion-like wounds it is more effective that whole BLF. The BLF C-lobe may be a novel therapeutic for the treatment of corneal lesions.