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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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

Detaljer

Författare
  • A. Sahaboglu
  • O. Paquet-Durand
  • J. Dietter
  • K. Dengler
  • S. Bernhard-Kurz
  • Per Ekström
  • B. Hitzmann
  • M. Ueffing
  • F. Paquet-Durand
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Artikelnummere488
TidskriftCell Death & Disease
Volym4
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa

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