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Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration

Sancho-Pelluz, J.; Arango-Gonzalez, B.; Kustermann, S.; Romero, F. J.; van Veen, Theo LU ; Zrenner, E.; Ekström, Per LU and Paquet-Durand, F. (2008) In Molecular Neurobiology 38(3). p.253-269
Abstract
Photoreceptor cell death is the major hallmark of a group of human inherited retinal degenerations commonly referred to as retinitis pigmentosa (RP). Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Previous research work has focused on apoptosis, but recent evidence suggests that photoreceptor cell death may result primarily from non-apoptotic mechanisms independently of AP1 or p53 transcription factor activity, Bcl proteins, caspases, or cytochrome c release. This review briefly describes some animal models used for studies of retinal degeneration, with particular focus on the rd1 mouse. After outlining the major features of different cell death... (More)
Photoreceptor cell death is the major hallmark of a group of human inherited retinal degenerations commonly referred to as retinitis pigmentosa (RP). Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Previous research work has focused on apoptosis, but recent evidence suggests that photoreceptor cell death may result primarily from non-apoptotic mechanisms independently of AP1 or p53 transcription factor activity, Bcl proteins, caspases, or cytochrome c release. This review briefly describes some animal models used for studies of retinal degeneration, with particular focus on the rd1 mouse. After outlining the major features of different cell death mechanisms in general, we then compare them with results obtained in retinal degeneration models, where photoreceptor cell death appears to be governed by, among other things, changes in cyclic nucleotide metabolism, downregulation of the transcription factor CREB, and excessive activation of calpain and PARP. Based on recent experimental evidence, we propose a putative non-apoptotic molecular pathway for photoreceptor cell death in the rd1 retina. The notion that inherited photoreceptor cell death is driven by non-apoptotic mechanisms may provide new ideas for future treatment of RP. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Retina, rd1, PARP, CREB, Oxidative stress, Calpain, cGMP, AIF, Calcium, rd2, rds, APOPTOSIS-INDUCING FACTOR, ROD CGMP-PHOSPHODIESTERASE, ENDOPLASMIC-RETICULUM STRESS, ELEMENT-BINDING PROTEIN, CAMP EARLY, REPRESSOR, RD1 MOUSE RETINA, MEDIATED PROGRAMMED NECROSIS, CALCIUM-CHANNEL BLOCKER, NITRIC-OXIDE SYNTHASE, D-CIS-DILTIAZEM
in
Molecular Neurobiology
volume
38
issue
3
pages
253 - 269
publisher
Humana Press
external identifiers
  • wos:000261598100004
  • scopus:59049100857
ISSN
1559-1182
DOI
10.1007/s12035-008-8045-9
language
English
LU publication?
yes
id
f2ab4d45-ad23-41e4-a819-ad50a4bb4636 (old id 1415765)
date added to LUP
2009-06-16 16:51:30
date last changed
2017-11-12 03:42:16
@article{f2ab4d45-ad23-41e4-a819-ad50a4bb4636,
  abstract     = {Photoreceptor cell death is the major hallmark of a group of human inherited retinal degenerations commonly referred to as retinitis pigmentosa (RP). Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Previous research work has focused on apoptosis, but recent evidence suggests that photoreceptor cell death may result primarily from non-apoptotic mechanisms independently of AP1 or p53 transcription factor activity, Bcl proteins, caspases, or cytochrome c release. This review briefly describes some animal models used for studies of retinal degeneration, with particular focus on the rd1 mouse. After outlining the major features of different cell death mechanisms in general, we then compare them with results obtained in retinal degeneration models, where photoreceptor cell death appears to be governed by, among other things, changes in cyclic nucleotide metabolism, downregulation of the transcription factor CREB, and excessive activation of calpain and PARP. Based on recent experimental evidence, we propose a putative non-apoptotic molecular pathway for photoreceptor cell death in the rd1 retina. The notion that inherited photoreceptor cell death is driven by non-apoptotic mechanisms may provide new ideas for future treatment of RP.},
  author       = {Sancho-Pelluz, J. and Arango-Gonzalez, B. and Kustermann, S. and Romero, F. J. and van Veen, Theo and Zrenner, E. and Ekström, Per and Paquet-Durand, F.},
  issn         = {1559-1182},
  keyword      = {Retina,rd1,PARP,CREB,Oxidative stress,Calpain,cGMP,AIF,Calcium,rd2,rds,APOPTOSIS-INDUCING FACTOR,ROD CGMP-PHOSPHODIESTERASE,ENDOPLASMIC-RETICULUM STRESS,ELEMENT-BINDING PROTEIN,CAMP EARLY,REPRESSOR,RD1 MOUSE RETINA,MEDIATED PROGRAMMED NECROSIS,CALCIUM-CHANNEL BLOCKER,NITRIC-OXIDE SYNTHASE,D-CIS-DILTIAZEM},
  language     = {eng},
  number       = {3},
  pages        = {253--269},
  publisher    = {Humana Press},
  series       = {Molecular Neurobiology},
  title        = {Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration},
  url          = {http://dx.doi.org/10.1007/s12035-008-8045-9},
  volume       = {38},
  year         = {2008},
}