Uncover of molecular mechanism underlying neuroprotective effects of PEDF peptides as therapeutic agents for inherited retinal degeneration

Retinitis pigmentosa (RP) is caused by loss of the cells that respond to light in the retina. Most forms of RP are today untreatable, and while individually they are rare, together they constitute a major cause of severe visual loss and blindness in the working age population. Because RP shows heterogeneous genetic features, neuroprotection, that targets common cell death mechanisms may benefit a high number of patients, independently from the individual mutation. We have identified a small peptide, H105A, from a natural protein present in the eye pigment epithelium-derived factor (PEDF), that can slow down degeneration in mouse models of RP but also in a human organoid model. In this project we plan to define the therapeutic window for H105A delivery to help the selection of patients based on the stage of retinal degeneration. Secondly, we plan to characterize the cells that are target of H105A in the treated retina. This information is important for the translation of the treatment to the clinic. The long-term goal of this proposal is the development of a treatment protocol for patients suffering from inherited retinal degeneration by targeting detrimental events activated in most forms of the disease.