Why study rod cell death in retinal degenerations and how?

Why study rod cell death in retinal degenerations and how? Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease. Recent anatomical studies using elegant innovative techniques reveal that there is a 30% rod loss in normal ageing, which is increased in early AMD. Those and other observations by Curcio and co-workers indicate that early rod loss is an important denominator of AMD (Curcio CA. Eye 2001; 15:376). As in retinitis pigmentosa (RP), rods appear to die by apoptosis. Thus it seems mandatory to study the regulation of rod cell death in animal models to unravel possible mechanisms of rod loss in AMD. Our laboratory investigates signal transduction pathways and gene regulation of rod death in our model of light-induced apoptosis. The transcription factor AP1 is essential, whereas other classical pro- and antiapoptotic genes appear to be less important in our model system. Caspase-1 gene expression is distinctly upregulated after light exposure and there are several factors which completely protect against light-induced cell death, such as the anesthetic halothane, dexamethasone and the absence of bleachable rhodopsin during light exposure. A fast rhodopsin regeneration rate increased damage susceptibility. Our data indicate that rhodopsin is essential for the initiation of light-induced rod loss. Following photon absorption, there may be the generation of photochemically active molecules wich then induce the apoptotic death cascade. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Documenta Ophthalmologica Springer Journals

Why study rod cell death in retinal degenerations and how?

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Publisher
Springer Journals
Copyright
Copyright © 2003 by Kluwer Academic Publishers
Subject
Medicine & Public Health; Ophthalmology
ISSN
0012-4486
eISSN
1573-2622
D.O.I.
10.1023/A:1022423724376
Publisher site
See Article on Publisher Site

Abstract

Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease. Recent anatomical studies using elegant innovative techniques reveal that there is a 30% rod loss in normal ageing, which is increased in early AMD. Those and other observations by Curcio and co-workers indicate that early rod loss is an important denominator of AMD (Curcio CA. Eye 2001; 15:376). As in retinitis pigmentosa (RP), rods appear to die by apoptosis. Thus it seems mandatory to study the regulation of rod cell death in animal models to unravel possible mechanisms of rod loss in AMD. Our laboratory investigates signal transduction pathways and gene regulation of rod death in our model of light-induced apoptosis. The transcription factor AP1 is essential, whereas other classical pro- and antiapoptotic genes appear to be less important in our model system. Caspase-1 gene expression is distinctly upregulated after light exposure and there are several factors which completely protect against light-induced cell death, such as the anesthetic halothane, dexamethasone and the absence of bleachable rhodopsin during light exposure. A fast rhodopsin regeneration rate increased damage susceptibility. Our data indicate that rhodopsin is essential for the initiation of light-induced rod loss. Following photon absorption, there may be the generation of photochemically active molecules wich then induce the apoptotic death cascade.

Journal

Documenta OphthalmologicaSpringer Journals

Published: Oct 6, 2004

References

  • An international classification and grading system for age-related maculopathy and age-related macular degeneration
    Bird, AC; Bressler, NM; Bressler, SB
  • Morphologic changes in age-related maculopathy
    Kliffen, M; van der Schaft, TL; Mooy, CM; de Jong, PT
  • Apoptotic cell death in retinal degenerations
    Reme, CE; Grimm, C; Hafezi, F; Marti, A; Wenzel, A
  • Apoptosis in the retina: the silent death of vision
    Reme, CE; Grimm, C; Hafezi, F; Wenzel, A; Williams, TP
  • Photoreversal of rhodopsin bleaching
    Williams, TP

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