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Alessandro Lambiase, Luigi Manni, Stefano Bonini, Paolo Rama, Alessandra Micera, Luigi Aloe; Nerve Growth Factor Promotes Corneal Healing: Structural, Biochemical, and Molecular Analyses of Rat and Human Corneas. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1063-1069.
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purpose. A recent clinical report demonstrated that topical nerve growth factor
(NGF) treatment in patients affected by corneal neurotrophic ulcers
induced epithelial and stromal healing restoring corneal integrity.
Mechanisms(s) undergoing these clinical NGF actions are still unclear.
The aim of this study was to investigate the role of NGF in human and
rat cornea physiopathology.
methods. Expression of high-affinity NGF receptors, NGF-mRNA, and NGF protein
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 cornea after an experimental model of epithelial injury, by means
of immunohistochemistry, in situ hybridization reverse
transcription–polymerase chain reaction, and enzyme-linked
results. The resultant data demonstrated that NGF is a constitutive
molecule present and produced in normal human and rat corneas. In vitro
human and rat corneal epithelial cells produce, store, and release NGF
and also express 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 injury. In vivo, after rat corneal
epithelial injury, a transient increase of corneal NGF levels was
observed. Inhibition of endogenous NGF activity by neutralizing
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 important
role in corneal physiopathology and suggest that this neurotrophin may
exert therapeutic action in wide-spectrum corneal
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