IOVS Drug Metabolism and Disposition
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2005;46:2601-2610.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0129
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Graham, D. R.
Right arrow Articles by Ash, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Graham, D. R.
Right arrow Articles by Ash, J. D.

Leukemia Inhibitory Factor Blocks Expression of Crx and Nrl Transcription Factors to Inhibit Photoreceptor Differentiation

Dianca R. Graham,1 Paul A. Overbeek,2 and John D. Ash1,3

3From the Department of Ophthalmology and the 1Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and the 2Department of Molecular and Cellular Biology and Ophthalmology, Baylor College of Medicine, Houston, Texas.

PURPOSE. Activating ligands of gp130, including leukemia inhibitory factor (LIF), can block differentiation and function of retinal neurons. This study focused on determining whether LIF inhibits differentiation of photoreceptors by altering cell fate or by blocking the expression of essential transcription factors in vivo.

METHODS. Transgenic mice were generated that had lens-specific expression of the secreted human LIF protein. Retinal differentiation was assessed by histology and by gene expression analysis, with in situ hybridization, immunohistochemistry, and real-time qRT-PCR. Electroretinograms were used to assess retinal function.

RESULTS. LIF did not prevent or alter the timing of outer and inner nuclear layer separation, but it inhibited phototransduction gene expression in both rods and cones, thereby blocking functional maturation of photoreceptors. LIF also reduced the expression of Crx, Nrl, and Nr2e3, and upregulated the expression of transcription inhibitors Baf and Fiz1.

CONCLUSIONS. LIF expression did not appear to alter photoreceptor cell fate specification, but it inhibited subsequent differentiation. These results suggest that gp130 ligands can inhibit photoreceptor functional differentiation by reducing Crx- and Nrl-dependent transcription.




This article has been cited by other articles:


Home page
 ReproductionHome page
S J Kimber, S F Sneddon, D J Bloor, A M El-Bareg, J A Hawkhead, A D Metcalfe, F D Houghton, H J Leese, A Rutherford, B A Lieberman, et al.
Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors
Reproduction, May 1, 2008; 135(5): 635 - 647.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. D. Rhee, A. Ruiz, J. L. Duncan, W. W. Hauswirth, M. M. LaVail, D. Bok, and X.-J. Yang
Molecular and Cellular Alterations Induced by Sustained Expression of Ciliary Neurotrophic Factor in a Mouse Model of Retinitis Pigmentosa
Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1389 - 1400.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. Samardzija, A. Wenzel, S. Aufenberg, M. Thiersch, C. Reme, and C. Grimm
Differential role of Jak-STAT signaling in retinal degenerations
FASEB J, November 1, 2006; 20(13): 2411 - 2413.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
F. Merhi-Soussi, B. Angenieux, K. Canola, C. Kostic, M. Tekaya, D. Hornfeld, and Y. Arsenijevic
High Yield of Cells Committed to the Photoreceptor Fate from Expanded Mouse Retinal Stem Cells
Stem Cells, September 1, 2006; 24(9): 2060 - 2070.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. Rothermel, K. Volpert, M. Burghardt, C. Lantzsch, A. A. Robitzki, and P. G. Layer
Knock-Down of GFR{alpha}4 Expression by RNA Interference Affects the Development of Retinal Cell Types in Three-Dimensional Histiotypic Retinal Spheres.
Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2716 - 2725.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Abou-Sleymane, F. Chalmel, D. Helmlinger, A. Lardenois, C. Thibault, C. Weber, K. Merienne, J.-L. Mandel, O. Poch, D. Devys, et al.
Polyglutamine expansion causes neurodegeneration by altering the neuronal differentiation program
Hum. Mol. Genet., March 1, 2006; 15(5): 691 - 703.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Association for Research in Vision and Ophthalmology