Temporal progression of PARP activity in the Prph2 mutant rd2 mouse: Neuroprotective effects of the PARP inhibitor PJ34

نویسندگان

  • Ayse Sahaboglu
  • Alaa Sharif
  • Lili Feng
  • Enver Secer
  • Eberhart Zrenner
  • François Paquet-Durand
چکیده

Peripherin (peripherin/rds) is a membrane-associated protein that plays a critical role in the morphogenesis of rod and cone photoreceptor outer segments. Mutations in the corresponding PRPH2 gene cause different types of retinal dystrophies characterized by a loss of photoreceptors. Over activation of poly-ADP-ribose polymerase (PARP) was previously shown to be involved in different animal models for hereditary retinal dystrophies. This includes the rd2 mouse, which suffers from a human homologous mutation in the PRPH2 gene. In the present study, we show that increased retinal PARP activity and poly-ADP-ribosylation of proteins occurs before the peak of rd2 photoreceptor degeneration. Inhibition of PARP activity with the well-characterized PARP inhibitor PJ34 decreased the levels of poly-ADP-ribosylation and photoreceptor cell death. These results suggest a causal involvement of PARP in photoreceptor degeneration caused by peripherin mutations and highlight the possibility to use PARP inhibition for the mutation-independent treatment of hereditary retinal dystrophies.

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عنوان ژورنال:

دوره 12  شماره 

صفحات  -

تاریخ انتشار 2017