Neuroprotection of Photoreceptor Degeneration

01/02/2017 to 31/01/2018

In inherited forms of retinal degeneration, the phototransduction cascade is non-functional due to mutation in photoreceptors (rod, cone) or in RPE. Non-functional PDE6 causes accumulation of cGMP and may trigger numerous signalling pathways such as over-activated poly (ADP) ribose polymerase (PARP) activation. PARP activation has recently been shown at the peak of degeneration for RP mouse and rat models and mutants characterized by a high number of TUNEL-positive cells also displayed high number of both PARP activity and PAR stained cells (Arango-Gonzalez et al. 2014).
In retinal explant cultures in vitro, several PARP inhibitors showed neuroprotection in inherited retinal degeneration models (Sahaboglu et al. 2016). But how PARP inhibition protects the photoreceptors is unclear. Therefore, understanding of molecular mechanism of neuroprotection by PARP inhibition will help to identify PARP related novel targets for therapy developments.