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Lingtao You, Friedrich E. Kruse, Hans E. Völcker; Neurotrophic Factors in the Human Cornea. Invest. Ophthalmol. Vis. Sci. 2000;41(3):692-702.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To investigate neurotrophic growth factors and corresponding receptors
in human and rabbit corneal epithelium and stroma.
methods. Transcription of nerve growth factor (NGF), neurotrophin 3 (NT-3),
NT-4, brain-derived neurotrophic factor (BDNF), glial cell
line–derived neurotrophic factor (GDNF), and receptors Trk
A–E, was investigated by reverse transcription–polymerase chain
reaction. DNA dot blot analysis allowed to estimate transcription
levels. Single cell proliferation assays were performed using
recombinant NGF, BDNF, and GDNF. Mitogen-activated protein kinase
signal transduction was investigated with Western blot analysis using
antibodies against activated and total extracellular signal-regulated
kinase (ERK) 1/2 and the jun N-terminal protein kinase (JNK) 1/2.
results. Transcription of NGF, NT-3, BDNF, and Trk A, Trk B, Trk C, and Trk E
receptors was detected in both ex vivo and cultured epithelium and
stroma. Transcription of NT-4 was only detected in epithelium and
transcription of GDNF only in stroma. Levels of transcription were
higher for NT-3, NT-4, and the Trk receptors and lower for NGF, BDNF,
and GDNF. NGF and GDNF stimulated both epithelial colony formation and
proliferation, whereas BDNF only enhanced colony formation. Stromal
proliferation was enhanced in serum-free medium. In epithelium,
predominantly ERK 1 was activated by NGF, GDNF, and BDNF. In stromal
cells NGF and GDNF stimulated phosphorylation of ERK 1 and JNK 1.
conclusions. Neurotrophic factors and tyrosine kinase receptors are transcribed in
the human cornea. GDNF and NGF stimulate corneal epithelial
proliferation, and the effect of the latter might be mediated by
activation of ERK 1. Neurotrophic factors have very specific effects on
phosphorylation of ERK and JNK in epithelial and stromal cells. The
differential expression of NT-4 and GDNF suggests a regulatory function
within the cytokine network of the cornea.
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