Retinitis pigmentosa (RP) is a group of inherited retinal degenerations for which no treatment is available. Despite their genetic heterogeneity, common mechanisms, like apoptosis, are responsible for photoreceptor cell death. This allows testing strategies aim at retarding or arresting apoptosis independently from the mutation causing the disease. Various molecules with neurotrophic activity are being evaluated for treatment of RP in animal models. In particular, we have explored the potential neurotrophic effect of Erythropoietin (Epo) by adeno-associated viral (AAV) vectors gene transfer to the retina and muscle of three RP models: the light-damaged albino Lewis rat, rds and rd10 mice. Interestingly, following systemic but not intraocular Epo delivery, morphological and functional photoreceptor protection was observed in the light-damage and rds models, thus suggesting that the Epo neurotrophic effect might not be exerted directly on the RP retina. To gain further insight into the mechanism of Epo photoreceptor protection we are currently characterizing Epo processing from AAV transduced muscle and retina which might account for their different neuroprotective properties. In addition, using AAV we are transfering to the retina of our models a chimeric Epo receptor (Fv2EpoR) which can be activated by a small dimerizer drug, AP20187. Upon AP20187 administration and Fv2EpoR activation the Epo signalling cascade is triggered in photoreceptors. This will help understand if Epo's retinal neuroprotection is direct and whether activation of the Epo pathway might be considered for therapy of some retinal degenerations.