Comparison of Nerve Growth Factor with Fetal Bovine Serum for Promoting Closure of Defects in Corneal Epithelial Cell...

Background: Disruption of the corneal epithelial (CE) cell layer is a pathological feature of several ocular disorders including the potentially severe condition, neurotrophic keratitis (NK). The drug, Oxervate™, whose active principle is recombinant human nerve growth factor (NGF), has been shown to promote healing of the corneal epithelial layer in NK. This effect could result from NGF stimulating the repair and regeneration of corneal nerves so that they provide better trophic support for CE healing and general health. Another mechanism of NGF in promoting CE layer healing may be through direct stimulation of the division and migration of CE cells. Fetal bovine serum (FBS) has also been found to promote CE layer healing in experimental studies. Like Oxervate™, FBS contains NGF, but it also contains several other bioactive components including other growth factors. The present study compares the effects of FBS to those of NGF to examine whether the combination of bioactive components in FBS might be more effective than NGF alone in producing corneal wound healing. Methods: CE cells of the HCE-S line were grown in 96-well plates fitted with a silicon plug that occluded a 1 mm circular area in the center of each well. When the cells reached confluence, the plugs were removed, resulting in the cell layers each containing a similar central defect. Different amounts of NGF, FBS, and a combination of the two were then added to each well. The effect of these treatments on the amount of closure of the defect after 24 h was measured and compared. Results: NGF increased the amount of closure of the defect after 24 h. At a concentration of 250 nM, NGF produced a significant, 25 ± 9% increase in closure. No further increase in effect was seen when the NGF concentration was increased to 500 nM. FBS also produced an increase in the closure. At an FBS concentration of 10%, this increase was 118 ± 27%, which was significantly greater than the percentage increase produced by NGF. The addition of both 250 nM NGF and 10% FBS together produced no greater amount of closure than that produced by FBS alone. Conclusions: These findings are consistent with earlier data suggesting that NGF can promote corneal healing through a direct effect on CE cells. They also show that FBS is more effective than NGF alone in producing this effect. Since the therapeutic activity of NGF in NK may be partly mediated through a direct action on corneal epithelial cells, identifying the factors in FBS that promote corneal healing might lead to more effective treatments for NK.