QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (63) Citing Articles via Google Scholar Google Scholar Articles by Wenzel, A. Articles by Remé, C. E. Search for Related Content PubMed PubMed Citation Articles by Wenzel, A. Articles by Remé, C. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB N-NITROSO-N-METHYLUREA

 Previous Article  |  Next Article 

The Journal of Neuroscience, January 1, 2000, 20(1):81-88

c-fos Controls the "Private Pathway" of Light-Induced Apoptosis of Retinal Photoreceptors

Andreas Wenzel¹, Christian Grimm¹, Andreas Marti¹, Nicole Kueng-Hitz², Farhad Hafezi¹, Günter Niemeyer², and Charlotte E. Remé¹

Department of Ophthalmology, Laboratories of ¹ Retinal Cell Biology and ² Neurophysiology, University Hospital Zürich, CH-8091 Zürich, Switzerland

White light (5 klux for 2 hr) induces apoptosis of rod photoreceptors in wild-type mice (c-fos^+/+) within 24 hr, whereas rods of c-fos knock-out mice (c-fos^/) are protected (Hafezi et al., 1997b).

The range of this protection was tested by analyzing retinas of c-fos^+/+ and c-fos^/ mice up to 10 d after exposure to threefold increased light intensities (15 klux for 2 hr). In c-fos^/ mice, rods were unaffected, whereas they were destroyed in c-fos^+/+ mice. After light exposure, mitochondrial damage in rods was observed exclusively in c-fos^+/+ mice. Electroretinograms recorded 48 hr after exposure revealed a decrease of all components in c-fos^+/+ mice but indicated no light-induced loss of function in c-fos^/ mice. Thus, in c-fos^/ mice, light-induced apoptosis is blocked or its threshold is elevated more than threefold.

Increased activity of the transcription factor activator protein-1 (AP-1) in retinas of light-exposed c-fos^+/+ mice indicated an acute contribution of AP-1 to apoptosis induction. AP-1 activity increased already during exposure and peaked ~6 hr thereafter, coinciding with the appearance of major morphological signs of apoptosis. Activated AP-1 mainly consisted of c-Fos/Jun heterodimers. In c-fos^/ mice, AP-1 activity remained unchanged, indicating that no other Jun- or Fos-family member could substitute for c-Fos. Like damaging light, N-methyl-N-nitrosourea (MNU) induced AP-1 containing c-Fos in c-fos^+/+ mice and did not induce AP-1 in c-fos^/ mice. In contrast to light, however, MNU induced apoptosis in rods of c-fos^/ mice. Thus, c-Fos is essential for a specific premitochondrial "private apoptotic pathway" induced by light but not for the execution of apoptosis induced by other stimuli.

Key words: retinal degeneration; photoreceptor; light damage; apoptosis; mitochondria; c-fos; AP-1; N-methyl-N-nitrosourea; mouse

---

Copyright © 2000 Society for Neuroscience  0270-6474/0/20181-08$05.00/0

This article has been cited by other articles:

				D. Gu, W. A. Beltran, Z. Li, G. M. Acland, and G. D. Aguirre Clinical Light Exposure, Photoreceptor Degeneration, and AP-1 Activation: A Cell Death or Cell Survival Signal in the Rhodopsin Mutant Retina? Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 4907 - 4918. [Abstract] [Full Text] [PDF]

				G.-H. Peng and S. Chen Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation Hum. Mol. Genet., October 15, 2007; 16(20): 2433 - 2452. [Abstract] [Full Text] [PDF]

				Y.-H. Wang, W.-T. Chiu, Y.-K. Wang, C.-C. Wu, T.-L. Chen, C.-F. Teng, W.-T. Chang, H.-C. Chang, and M.-J. Tang Deregulation of AP-1 Proteins in Collagen Gel-induced Epithelial Cell Apoptosis Mediated by Low Substratum Rigidity J. Biol. Chem., January 5, 2007; 282(1): 752 - 763. [Abstract] [Full Text] [PDF]

				M. Samardzija, A. Wenzel, M. Thiersch, R. Frigg, C. Reme, and C. Grimm Caspase-1 Ablation Protects Photoreceptors in a Model of Autosomal Dominant Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5181 - 5190. [Abstract] [Full Text] [PDF]

				M A Mainster Violet and blue light blocking intraocular lenses: photoprotection versus photoreception Br. J. Ophthalmol., June 1, 2006; 90(6): 784 - 792. [Abstract] [Full Text] [PDF]

				C. E. Reme The Dark Side of Light: Rhodopsin and the Silent Death of Vision The Proctor Lecture Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2672 - 2682. [Full Text] [PDF]

				A. V. Cideciyan, S. G. Jacobson, T. S. Aleman, D. Gu, S. E. Pearce-Kelling, A. Sumaroka, G. M. Acland, and G. D. Aguirre In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa PNAS, April 5, 2005; 102(14): 5233 - 5238. [Abstract] [Full Text] [PDF]

				M. Tanito, Y.-W. Kwon, N. Kondo, J. Bai, H. Masutani, H. Nakamura, J. Fujii, A. Ohira, and J. Yodoi Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage J. Neurosci., March 2, 2005; 25(9): 2396 - 2404. [Abstract] [Full Text] [PDF]

				H. Tomita, Y. Kotake, and R. E. Anderson Mechanism of Protection from Light-Induced Retinal Degeneration by the Synthetic Antioxidant Phenyl-N-tert-Butylnitrone Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 427 - 434. [Abstract] [Full Text] [PDF]

				M. Ettaiche, N. Guy, P. Hofman, M. Lazdunski, and R. Waldmann Acid-Sensing Ion Channel 2 Is Important for Retinal Function and Protects against Light-Induced Retinal Degeneration J. Neurosci., February 4, 2004; 24(5): 1005 - 1012. [Abstract] [Full Text] [PDF]

				M A Mainster and J R Sparrow How much blue light should an IOL transmit? Br. J. Ophthalmol., December 1, 2003; 87(12): 1523 - 1529. [Abstract] [Full Text] [PDF]

				D. Petrin, A. Baker, S. G. Coupland, P. Liston, M. Narang, K. Damji, B. Leonard, V. A. Chiodo, A. Timmers, W. Hauswirth, et al. Structural and Functional Protection of Photoreceptors from MNU-Induced Retinal Degeneration by the X-Linked Inhibitor of Apoptosis Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2757 - 2763. [Abstract] [Full Text] [PDF]

				A. Wenzel, C. Grimm, M. Samardzija, and C. E. Reme The Genetic Modifier Rpe65Leu450: Effect on Light Damage Susceptibility in c-Fos-Deficient Mice Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2798 - 2802. [Abstract] [Full Text] [PDF]

				D. T. Organisciak, R. M. Darrow, L. Barsalou, R. K. Kutty, and B. Wiggert Susceptibility to Retinal Light Damage in Transgenic Rats with Rhodopsin Mutations Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 486 - 492. [Abstract] [Full Text] [PDF]

				T. Wu, Y. Chen, S. K. S. Chiang, and M. O. M. Tso NF-{kappa}B Activation in Light-Induced Retinal Degeneration in a Mouse Model Invest. Ophthalmol. Vis. Sci., September 1, 2002; 43(9): 2834 - 2840. [Abstract] [Full Text] [PDF]

				M. Tanito, A. Nishiyama, T. Tanaka, H. Masutani, H. Nakamura, J. Yodoi, and A. Ohira Change of Redox Status and Modulation by Thiol Replenishment in Retinal Photooxidative Damage Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2392 - 2400. [Abstract] [Full Text] [PDF]

				T. Oshitari, M. Dezawa, S. Okada, M. Takano, H. Negishi, H. Horie, H. Sawada, T. Tokuhisa, and E. Adachi-Usami The Role of c-fos in Cell Death and Regeneration of Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2442 - 2449. [Abstract] [Full Text] [PDF]

				K. Shinoda, Y. Nakamura, K. Matsushita, K. Shimoda, H. Okita, M. Fukuma, T. Yamada, H. Ohde, Y. Oguchi, J.-i. Hata, et al. Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene Br. J. Ophthalmol., October 1, 2001; 85(10): 1237 - 1243. [Abstract] [Full Text] [PDF]

				A. Wenzel, C. Grimm, M. W. Seeliger, G. Jaissle, F. Hafezi, R. Kretschmer, E. Zrenner, and C. E. Remé Prevention of Photoreceptor Apoptosis by Activation of the Glucocorticoid Receptor Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1653 - 1659. [Abstract] [Full Text]

				C. Keller, C. Grimm, A. Wenzel, F. Hafezi, and C. E. Remé Protective Effect of Halothane Anesthesia on Retinal Light Damage: Inhibition of Metabolic Rhodopsin Regeneration Invest. Ophthalmol. Vis. Sci., February 1, 2001; 42(2): 476 - 480. [Abstract] [Full Text]

				C. Grimm, A. Wenzel, T. P. Williams, P. O. Rol, F. Hafezi, and C. E. Remé Rhodopsin-Mediated Blue-Light Damage to the Rat Retina: Effect of Photoreversal of Bleaching Invest. Ophthalmol. Vis. Sci., February 1, 2001; 42(2): 497 - 505. [Abstract] [Full Text]

				J. Yang, R. Gross, S. Basinger, and S. Wu Apoptotic cell death of cultured salamander photoreceptors induced by cccp: CsA-insensitive mitochondrial permeability transition J. Cell Sci., January 5, 2001; 114(9): 1655 - 1664. [Abstract] [PDF]

				A. Fleischmann, F. Hafezi, C. Elliott, C. E. Remé, U. Rüther, and E. F. Wagner Fra-1 replaces c-Fos-dependent functions in mice Genes & Dev., November 1, 2000; 14(21): 2695 - 2700. [Abstract] [Full Text]

				F HAFEZI, C GRIMM, B C SIMMEN, A WENZEL, and C E REMÉ Molecular ophthalmology: an update on animal models for retinal degenerations and dystrophies Br. J. Ophthalmol., August 1, 2000; 84(8): 922 - 927. [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help