Retinitis pigmentosa and retinal degenerations: deciphering pathways and targets for drug discovery and development

Inherited retinal diseases (IRDs) are a group of retinopathies generally caused by genetic mutations. Retinitis pigmentosa (RP) represents one of the most studied IRDs. RP leads to intense vision loss or blindness resulting from the degeneration of photoreceptor cells. To date, RP is mainly treated with palliative supplementation of vitamin A and retinoids, gene therapies, or surgical interventions. Therefore, a pharmacologically based therapy is an urgent need requiring a medicinal chemistry approach, to validate molecular targets able to deal with retinal degeneration. This Review aims at outlining the recent research efforts in identifying new drug targets for RP, especially focusing on the neuroprotective role of the Wnt/β-catenin/GSK3β pathway and apoptosis modulators (in particular PARP-1) but also on growth factors such as VEGF and BDNF. Furthermore, the role of spatiotemporally expressed G protein-coupled receptors (GPR124) in the retina and the emerging function of histone deacetylase inhibitors in promoting retinal neuroprotection will be discussed.