Nerve growth factor promotes corneal healing: Structural, biochemical, andmolecular analyses of rat and human corneas

PURPOSE. A recent clinical report demonstrated that topical nerve growth fa ctor (NGF) treatment in patients affected by corneal neurotrophic ulcers in duced epithelial and stromal healing restoring corneal integrity. Mechanism s(s) undergoing these clinical NGF actions are still unclear. The aim of th is study was to investigate the role of NGF in human and rat cornea physiop athology. METHODS. Expression of high-affinity NGF receptors, NGF-mRNA, and NGF prote in was evaluated in human and rat normal corneas, in human and rat corneal epithelial cell cultures, in human corneal organ culture, and in the rat co rnea after an experimental model of epithelial injury, by means of immunohi stochemistry, in situ hybridization reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS. The resultant data demonstrated that NGF is a constitutive molecul e present and produced in normal human and rat corneas. In vitro human and rat corneal epithelial cells produce, store, and release NGF and also expre ss high-affinity NGF receptors (TrkA). In human organ culture, epithelium, keratocytes, and endothelium have been shown to bind exogenous radiolabeled NGF, and the epithelial cells' binding was increased after epithelium inju ry. In vivo, after rat corneal epithelial injury, a transient increase of c orneal NGF levels was observed. Inhibition of endogenous NGF activity by ne utralizing anti-NGF antibodies delayed the corneal epithelial healing rate, whereas exogenous administration of NGF accelerated healing. CONCLUSIONS. Taken together, the above findings show that NGF plays an impo rtant role in corneal physiopathology and suggest that this neurotrophin ma y exert therapeutic action in wide-spectrum corneal diseases.