Pigment Epithelium-derived Factor (PEDF) peptides as therapeutic agents for inherited retinal degeneration

Retinal degenerations and among them retinitis pigmentosa, are caused by loss of the cells responding to light in the retina. Most forms of inherited retinal degenerations 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 retinitis pigmentosa shows heterogeneous genetic features, characterization and target of common molecular pathways may benefit several patients. The long-term goal of this proposal is the development of a drug and treatment protocol for several groups of patients suffering from inherited retinal degenerations by targeting detrimental events activated in most forms of the disease. We plan to develop therapeutic approaches based on pigment epithelium derived factor (PEDF), a potent neuroprotective protein naturally present in the retina. Specifically, we will evaluate small synthetic peptides derived from PEDF as protective agents using molecular and functional studies in vitro and in vivo. Small peptide molecules present advantages over large proteins as they limit side effects due to biological functions owned by other regions of PEDF. The proposal is significant because it can lead to the identification of second generation PEDF with enhanced retino-protective activity, which can be utilized with ocular delivery systems to delay photoreceptor degeneration that leads to blindness, and ultimately generate novel treatments for retinitis pigmentosa.