Document Detail


Ciliary neurotrophic factor: a survival and differentiation inducer in human retinal progenitors.
MedLine Citation:
PMID:  20428961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinitis pigmentosa, age-related macular degeneration, and Parkinson's disease remain major problems in the field of medicine. Some of the strategies being explored for treatment include replacement of damaged tissue by transplantation of healthy tissues or progenitor cells and delivery of neurotrophins to rescue degenerating tissue. One of the neurotrophins with promise is the ciliary neurotrophic factor (CNTF). In this study, we report the role played by CNTF in retinal cell differentiation and survival in retinal progenitors. We found that CNTF is a survival factor for multipotential human retinal cells and increased cell survival by 50%, over a 7-d period, under serum-free conditions, as determined by apoptotic assays (immunohistochemistry and flow cytometry). This effect is dose dependent with a maximum survival at a CNTF concentration of 20 ng/ml. We also report that CNTF might be a cell commitment factor, directing the differentiation mainly toward large multipolar cells with ganglionic and amacrine phenotype. These cells express tyrosine hydroxylase (amacrine cells) as well as, thy 1.1 and neuron-specific enolase (ganglionic cells). Additionally, there was also an increase in protein kinase C alpha, a protein expressed in rod and cone bipolars as well as cone photoreceptors and calbindin, a protein expressed in cone photoreceptors and horizontal cells. In our studies, CNTF doubled the number of cells with ganglionic phenotypes, and basic fibroblast growth factor doubled the number of cells with photoreceptor phenotype. Additionally, CNTF induced a subset of progenitors to undergo multiple rounds of cell division before acquiring the large multipolar ganglionic phenotype. Our conclusion is that CNTF could be an agent that has therapeutic potential and possibly induces differentiation of large multipolar ganglionic phenotype in a subset of progenitors.
Authors:
Kamla Dutt; Yang Cao; Ifeoma Ezeonu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-04-29
Journal Detail:
Title:  In vitro cellular & developmental biology. Animal     Volume:  46     ISSN:  1543-706X     ISO Abbreviation:  In Vitro Cell. Dev. Biol. Anim.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-11-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9418515     Medline TA:  In Vitro Cell Dev Biol Anim     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  635-46     Citation Subset:  IM    
Affiliation:
Department of Pathology, Morehouse School of Medicine, 720 Westview Drive, S.W., Atlanta, GA 30310-1495, USA. kdutt@msm.edu
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Blotting, Western
Cell Count
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cell Survival / drug effects
Cells, Cultured
Ciliary Neurotrophic Factor / pharmacology*
Fibroblast Growth Factor 2 / pharmacology
Humans
Immunohistochemistry
Microscopy, Phase-Contrast
Mitogens / pharmacology
Retina / cytology*
Stem Cells / cytology*,  drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
5 G12RR03034/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Ciliary Neurotrophic Factor; 0/Mitogens; 103107-01-3/Fibroblast Growth Factor 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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