Document Detail

The absence of c-fos prevents light-induced apoptotic cell death of photoreceptors in retinal degeneration in vivo.
MedLine Citation:
PMID:  9055866     Owner:  NLM     Status:  MEDLINE    
Apoptotic cell death in the retina was recently demonstrated in animal models of the hereditary human retinal dystrophy known as retinitis pigmentosa. Although recent evidence indicates that the proto-oncogene c-fos is a mediator of apoptosis, its precise role is unclear. In fact, under some conditions, c-fos may even protect against apoptotic cell death. In the retina, c-fos is physiologically expressed in a diurnal manner and is inducible by light. We previously observed a light-elicited, dose-dependent apoptotic response in rat photoreceptors. To determine whether c-fos is involved in the light-induced apoptotic pathway we have used control mice and mice lacking c-fos. We found that following dark adaptation and two hours of light exposure both groups of animals exhibited only a few apoptotic cells. However, at 12 and 24 additional hours after light exposure, apoptosis increased dramatically in controls but was virtually absent in those mice lacking c-fos. Therefore, c-fos is essential for light-induced apoptosis of photoreceptors. Notably, c-fos is continuously upregulated concomitant with apoptotic photoreceptor death in our system and in animal models of retinitis pigmentosa (Agarwal, N. et al., Invest. Ophthalmol. Vis.Sci. Suppl. 36, S638 and Rich, K.A. et al., Invest. Ophthalmol. Vis. Sci. Suppl. 35, 1833). Inhibition of c-fos expression might therefore represent a novel therapeutic strategy to retard the time course of retinal dystrophies and light-induced retinal degeneration.
F Hafezi; J P Steinbach; A Marti; K Munz; Z Q Wang; E F Wagner; A Aguzzi; C E Remé
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature medicine     Volume:  3     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-01     Completed Date:  1997-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  346-9     Citation Subset:  IM    
Department of Ophthalmology, University Clinic, Zurich, Switzerland.
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MeSH Terms
Apoptosis / genetics*
Gene Expression Regulation*
Genes, fos*
Mice, Knockout
Retinal Degeneration / genetics,  pathology*
Comment In:
Nat Med. 1997 Mar;3(3):280   [PMID:  9055852 ]

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