Advanced

How Long Does a Photoreceptor Cell Take to Die? Implications for the Causative Cell Death Mechanisms

Paquet-Durand, F.; Sahaboglu, A.; Dietter, J.; Paquet-Durand, O.; Hitzmann, B.; Ueffing, M. and Ekström, Per LU (2014) In Advances in Experimental Medicine and Biology 801. p.575-581
Abstract
The duration of cell death may allow deducing the underlying degenerative mechanism. To find out how long a photoreceptor takes to die, we used the rdl mouse model for retinal neurodegeneration, which is characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cGMP levels. Based on cellular data on the progression of cGMP accumulation, cell death, and survival, we created a mathematical model to simulate the temporal development of the degeneration and the clearance of dead cells. Both cellular data and modelling suggested that at the level of the individual cell, the degenerative process was rather slow, taking around 80 h to complete. Organotypic retinal explant cultures derived from wild-type... (More)
The duration of cell death may allow deducing the underlying degenerative mechanism. To find out how long a photoreceptor takes to die, we used the rdl mouse model for retinal neurodegeneration, which is characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cGMP levels. Based on cellular data on the progression of cGMP accumulation, cell death, and survival, we created a mathematical model to simulate the temporal development of the degeneration and the clearance of dead cells. Both cellular data and modelling suggested that at the level of the individual cell, the degenerative process was rather slow, taking around 80 h to complete. Organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast, confirmed the surprisingly long duration of an individual photoreceptor cell's death. We briefly discuss the possibility to link different cell death stages and their temporal progression to specific enzymatic activities known to be causally connected to cell death. This in turn opens up new perspectives for the treatment of inherited retinal degeneration, both in terms of therapeutic targets and temporal windows-of-opportunity. (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, cGMP, PKG, CNG channel, HDAC, PARP
in
Advances in Experimental Medicine and Biology
volume
801
pages
575 - 581
publisher
Kluwer
external identifiers
  • wos:000350418200074
  • scopus:84904787741
ISSN
0065-2598
DOI
10.1007/978-1-4614-3209-8_73
language
English
LU publication?
yes
id
e8d986a8-bb96-473c-b266-7696bd7efa64 (old id 5300338)
date added to LUP
2015-05-04 08:35:17
date last changed
2017-01-25 12:55:03
@article{e8d986a8-bb96-473c-b266-7696bd7efa64,
  abstract     = {The duration of cell death may allow deducing the underlying degenerative mechanism. To find out how long a photoreceptor takes to die, we used the rdl mouse model for retinal neurodegeneration, which is characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cGMP levels. Based on cellular data on the progression of cGMP accumulation, cell death, and survival, we created a mathematical model to simulate the temporal development of the degeneration and the clearance of dead cells. Both cellular data and modelling suggested that at the level of the individual cell, the degenerative process was rather slow, taking around 80 h to complete. Organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast, confirmed the surprisingly long duration of an individual photoreceptor cell's death. We briefly discuss the possibility to link different cell death stages and their temporal progression to specific enzymatic activities known to be causally connected to cell death. This in turn opens up new perspectives for the treatment of inherited retinal degeneration, both in terms of therapeutic targets and temporal windows-of-opportunity.},
  author       = {Paquet-Durand, F. and Sahaboglu, A. and Dietter, J. and Paquet-Durand, O. and Hitzmann, B. and Ueffing, M. and Ekström, Per},
  issn         = {0065-2598},
  keyword      = {TUNEL,Apoptosis,Necrosis,cGMP,PKG,CNG channel,HDAC,PARP},
  language     = {eng},
  pages        = {575--581},
  publisher    = {Kluwer},
  series       = {Advances in Experimental Medicine and Biology},
  title        = {How Long Does a Photoreceptor Cell Take to Die? Implications for the Causative Cell Death Mechanisms},
  url          = {http://dx.doi.org/10.1007/978-1-4614-3209-8_73},
  volume       = {801},
  year         = {2014},
}