Abstract:

To study the therapeutic effect of topically applied keratinocyte growth factor-2 (KGF-2) in vivo on corneal epithelial wound in rabbit model of alkali burn and explore new methods of treatment in the early of corneal epithelial wound. Methods A 6 mm diameter epithelial defect was made in the center of rabbit corneas by the alkali-soaked filter paper.A total of 60 Japanese white rabbits were randomly divided into two groups(n=30): KGF-2 group (25  mg/L) and control group. A 50 μL aliquot of 25 mg/L recombinant human KGF-2 was then applied topically three times a day. The same volume of phosphate-buffered saline (PBS) vehicle was applied to the control.Each corneal epithelial defect was subsequently photographed with a slit lamp on day 7 and 14 after burn and was measured by a computer-assisted digitizer.Corneal neovascularization in two groups was observed every day.The viability of corneal  epithelial cells   was assessed by MTT assay;meanwhile,the corneal epithelium was examined by morphometric and histological analysis.Results There were statistically significant differences in the epithelial defet area on day 7 and 14 between KGF-2 and control groups(p<0.01).The differences in corneal neovascularization (CNV) between KGF-2 and control  groups were also evident on day 7 and 14, the average percentages of CNV in KGF-2- group were 7.32% and 32.50%,whereas the rates in control group were 17.50% and 41.67%,respectively.On day 7 and 14 after wounding,there were statistically significant differences in the mean 570 nm absorbances between KGF-2 and control groups(P<0.05 or P<0.01).Histological examination showed that the corneal lesions consisted of stromal edema,keratocyte loss,inflammatory cell infiltration,and CNV.Corneal epithelium cell desquamation,stromal edema and numerous neutrophil infiltrations were present in the corneal stroma in control group.In contrast,the KGF-2 group exhibited no corneal stroma inflammation,only mild stromal edema remained in KGF-2 corneas on day 14 and the significant changes of the re-epithelialization in KGF-2 group were observed.Conclusion  Topically applied 25 mg/L KGF-2 can accelerate corneal epithelial wound healing,in contrast to the control,and reduce inflammation,stromal edema,and fibrosis.In addition,it also exhibites significant inhibition on CNV.KGF-2 maybe become another important growth factor in the regulation of corneal epithelial wound healing.

Key words: keratinocyte growth factor-2;corneal;epithelium;wound healing