PMID- 17982417
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20220310
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 13
DP  - 2007 Oct 16
TI  - Patterned expression of neurotrophic factors and receptors in human limbal and 
      corneal regions.
PG  - 1934-41
AB  - PURPOSE: To evaluate the expression patterns of neurotrophic factors (NTFs) and 
      their receptors in the human cornea with the intention of exploring the role of 
      NTFs in maintaining corneal epithelial stem cells in the limbus. METHODS: Fresh 
      human corneoscleral tissues were prepared for frozen sections. Immunofluorescent 
      staining was performed with primary antibodies against six members of three NTF 
      families and their six receptors. To confirm the specificity of NTF primary 
      antibodies, neutralization experiments with their corresponding peptides and 
      western blot analysis were performed. RESULTS: Based on spatial and differential 
      immuno-localization, three patterns of NTF expression were potentially involved 
      in epithelial-mesenchymal interaction on the ocular surface: (1) the epithelial 
      type: nerve growth factor (NGF) and glial cell-derived neurotrophic factor 
      (GDNF); (2) the paracrine type: neurotrophin (NT)-3 and NT-4/5; and (3) the 
      reciprocal type: brain-derived neurotrophic factor (BDNF). The stem cell-enriched 
      basal cells of the limbal epithelium expressed three unique staining patterns for 
      NTFs: (1) exclusively positive for NGF, GDNF, and their corresponding receptors, 
      TrkA and GDNF family receptor alpha (GFRalpha)-1; (2) relatively high levels of 
      BDNF; and (3) negative for NT-3 and NT-4. Additionally, the neurotrophin common 
      low-affinity receptor, p75NTR, was mainly expressed by the basal layer of the 
      entire corneal and limbal epithelia, and TrkB and TrkC were evenly expressed by 
      the entire corneal and limbal epithelia. BDNF, p75NTR, TrkB, and TrkC are also 
      abundantly expressed by limbal stroma cells. No specific immunoreactivity to 
      ciliary neurotrophic factor (CNTF) and its receptor, CNTFRalpha, was detected in 
      cornea tissue in situ. CONCLUSIONS: Our findings revealed patterned expression of 
      NTFs and their receptors in the human ocular surface, suggesting that they may 
      play a vital role in maintaining corneal epithelial stem cells in the limbus. 
      NGF, GDNF, GFRalpha-1, TrkA, and BDNF may serve as new limbal basal cell markers 
      defining the corneal epithelial stem cell phenotype.
FAU - Qi, Hong
AU  - Qi H
AD  - Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor 
      College of Medicine, Houston, TX 77030, USA.
FAU - Chuang, Eliseu Yung
AU  - Chuang EY
FAU - Yoon, Kyung-Chul
AU  - Yoon KC
FAU - de Paiva, Cintia S
AU  - de Paiva CS
FAU - Shine, H David
AU  - Shine HD
FAU - Jones, Dan B
AU  - Jones DB
FAU - Pflugfelder, Stephen C
AU  - Pflugfelder SC
FAU - Li, De-Quan
AU  - Li DQ
LA  - eng
GR  - NS35280/NS/NINDS NIH HHS/United States
GR  - EY11915/EY/NEI NIH HHS/United States
GR  - R03 EY014553-03/EY/NEI NIH HHS/United States
GR  - R03 EY014553/EY/NEI NIH HHS/United States
GR  - R01 EY011915/EY/NEI NIH HHS/United States
GR  - EY014553/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071016
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor Receptors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Nerve Growth Factor)
SB  - IM
MH  - Blotting, Western
MH  - Cornea/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Limbus Corneae/*metabolism
MH  - Nerve Growth Factors/*metabolism
MH  - Receptors, Nerve Growth Factor/*metabolism
MH  - Tissue Distribution
PMC - PMC2185513
EDAT- 2007/11/06 09:00
MHDA- 2007/12/07 09:00
PMCR- 2007/01/01
CRDT- 2007/11/06 09:00
PHST- 2007/06/13 00:00 [received]
PHST- 2007/10/12 00:00 [accepted]
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
PHST- 2007/01/01 00:00 [pmc-release]
AID - v13/a218 [pii]
AID - 218 [pii]
AID - 2007MOLVIS0185 [pii]
PST - epublish
SO  - Mol Vis. 2007 Oct 16;13:1934-41.