Rasagiline interferes with neurodegeneration in the Prph2/rds mouse

Retina. 2012 Mar;32(3):617-28. doi: 10.1097/IAE.0b013e31821e2070.

Abstract

Purpose: Rasagiline (N-propargyl-1(R)-aminoindan) is a second-generation propargylamine with neuroprotective effects. We used the Prph2/rds mouse to assess the effect of rasagiline on photoreceptor cell death and to examine the possible modulation of different pathways of programmed cell death.

Methods: The animals were orally treated with various doses of rasagiline from Postnatal Day 1 to 56. Methodological approaches consisted of morphometric analyses of the outer nuclear layer thickness and investigation of apoptotic events using TUNEL (TdT-mediated dUTP-biotin nick end labeling) assay, immunohistochemistry, and immunoblot staining. The expression of programmed cell death marker genes involved in photoreceptor degeneration was studied by quantitative real-time polymerase chain reaction.

Results: In the Prph2/rds mouse, treatment resulted in a significant dose-dependent neuroprotection at Postnatal Day 56 and a delay in the induction of apoptotic events at Postnatal Day 14. Programmed cell death marker gene expression showed that several mechanisms were involved in photoreceptor degeneration. Furthermore, rasagiline did not only target apoptosis but also other pathways such as autophagy and inflammation.

Conclusion: This study showed for the first time significant neuroprotective effects of rasagiline in the retina of Prph2/rds mice through caspase-dependent pathways. However, the activation of caspase-independent programmed cell death pathways that are not affected by rasagiline eventually led to retinal degeneration, but in a delayed manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Death / drug effects
  • Disease Models, Animal
  • Immunohistochemistry
  • Indans / administration & dosage
  • Indans / pharmacology*
  • Mice
  • Mice, Transgenic
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Real-Time Polymerase Chain Reaction
  • Retinal Degeneration / drug therapy*
  • Retinal Photoreceptor Cell Outer Segment / drug effects

Substances

  • Indans
  • Neuroprotective Agents
  • rasagiline