Advanced

Retinitis pigmentosa: rapid neurodegeneration is governed by slow cell death mechanisms

Sahaboglu, A.; Paquet-Durand, O.; Dietter, J.; Dengler, K.; Bernhard-Kurz, S.; Ekström, Per LU ; Hitzmann, B.; Ueffing, M. and Paquet-Durand, F. (2013) In Cell Death & Disease 4.
Abstract
For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosinemono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling... (More)
For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosinemono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling for the first time delineated three major cell death phases in a complex neuronal tissue: (1) initiation, taking up to 36 h, (2) execution, lasting another 40 h, and finally (3) clearance, lasting about 7 h. Surprisingly, photoreceptor neurodegeneration was noticeably slower than necrosis or apoptosis, suggesting a different mechanism of death for these neurons. Cell Death and Disease (2013) 4, e488; doi: 10.1038/cddis.2013.12; published online 7 February 2013 (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TUNEL, apoptosis, necrosis, retina, cGMP
in
Cell Death & Disease
volume
4
publisher
Nature Publishing Group
external identifiers
  • wos:000315769500008
  • scopus:84875993536
ISSN
2041-4889
DOI
10.1038/cddis.2013.12
language
English
LU publication?
yes
id
db893923-b929-4c86-a403-35ca6d420d59 (old id 3657445)
date added to LUP
2013-05-02 09:02:08
date last changed
2019-10-15 04:39:02
@article{db893923-b929-4c86-a403-35ca6d420d59,
  abstract     = {For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosinemono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling for the first time delineated three major cell death phases in a complex neuronal tissue: (1) initiation, taking up to 36 h, (2) execution, lasting another 40 h, and finally (3) clearance, lasting about 7 h. Surprisingly, photoreceptor neurodegeneration was noticeably slower than necrosis or apoptosis, suggesting a different mechanism of death for these neurons. Cell Death and Disease (2013) 4, e488; doi: 10.1038/cddis.2013.12; published online 7 February 2013},
  articleno    = {e488},
  author       = {Sahaboglu, A. and Paquet-Durand, O. and Dietter, J. and Dengler, K. and Bernhard-Kurz, S. and Ekström, Per and Hitzmann, B. and Ueffing, M. and Paquet-Durand, F.},
  issn         = {2041-4889},
  keyword      = {TUNEL,apoptosis,necrosis,retina,cGMP},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Cell Death & Disease},
  title        = {Retinitis pigmentosa: rapid neurodegeneration is governed by slow cell death mechanisms},
  url          = {http://dx.doi.org/10.1038/cddis.2013.12},
  volume       = {4},
  year         = {2013},
}