• retinitis pigmentosa environmental enrichment

Sensory experience plays a key role in the development and functioning of neuronal circuitries in the brain. In this thesis, we evaluated whether environmental enrichment (EE), a non-invasive condition of enhanced sensory stimulation and social interaction, promotes the recovery of visual functions in a murine model of retinitis pigmentosa (RP) (i.e., the Royal College of Surgeons rats). Using in vivo electrophysiology, we found that exposing 60 days old blind animals to one month of EE rescues visual responses to a certain extent of the inner retina. Both pattern electroretinograms (p-ERG) and oscillatory potentials (OP) were significantly enhanced; this occurring in parallel to a marked loss of full field electroretinogram (f-ERG) signal, both scotopic and photopic. Interestingly, multifocal electroretinogram (mfERG) increased significantly in RCS rats after EE. This was accompanied by a behavioral enhancement of light sensitivity and spatial resolution, assessed by light-dark box test and the optomotor response, respectively, in the same animals. The electrophysiological and behavioral recovery of visual functions paralleled a significant increase in the density and length of blood vessels at retinal level, as evaluated by fluorescence microscopy. RT-qPCR analysis revealed that these animals showed enhanced VEGF and eNOS levels in the retina, compared to nonenriched counterparts. Our findings support the application of this non-invasive protocol (EE), alone or in combination with other therapeutic approaches, to rescue visual functions in degenerative blindness.