Exploring PEDF as therapeutic agent for retinitis pigmentosa

Retinal degenerations and among them retinitis Pigmentosa (RP) are caused by loss of the cells responding to light in the retina. The molecular mechanism causing cell death of photoreceptors in the retina is still not well known despite the identification of many genes mutated in these diseases. 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 such 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. In collaboration with NIH-NEI we propose to characterize the molecular pathways targeted by the pigment epithelial derived factor (PEDF), a potent neuroprotective protein naturally present in the retina. We will also evaluate small synthetic peptides derived from PEDF as therapeutic 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 peptide regions of PEDF. The proposal is significant because it can lead to the identification of second generation PEDF with enhanced retinoprotective activity, which can be utilized in ocular delivery systems to delay photoreceptor degeneration that leads to blindness, and ultimately generate novel treatments for RP.