PMID- 10711683
OWN - NLM
STAT- MEDLINE
DCOM- 20000315
LR  - 20091119
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 41
IP  - 3
DP  - 2000 Mar
TI  - Neurotrophic factors in the human cornea.
PG  - 692-702
AB  - 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.
FAU - You, L
AU  - You L
AD  - Department of Ophthalmology, University of Heidelberg Medical School, Germany.
FAU - Kruse, F E
AU  - Kruse FE
FAU - Volcker, H E
AU  - Volcker HE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (DNA Primers)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Messenger)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques
MH  - Cell Division/drug effects
MH  - Cornea/cytology/*metabolism
MH  - DNA Primers/chemistry
MH  - Epithelial Cells/metabolism
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Nerve Growth Factors/*genetics/metabolism/pharmacology
MH  - Phosphorylation
MH  - RNA/isolation & purification
MH  - RNA, Messenger/*metabolism
MH  - Rabbits
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic
EDAT- 2000/03/11 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/03/11 09:00
PHST- 2000/03/11 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/03/11 09:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2000 Mar;41(3):692-702.