Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.

Purpose: This review explores the role of pigment epithelium-derived factor (PEDF) in retinal degenerative and vascular disorders and assesses its potential both as an adjunct to established vascular endothelial growth factor inhibiting treatments for retinal vascular diseases and as a neuroprotective therapeutic agent. Methods: A comprehensive literature review was conducted, focusing on the neuroprotective and anti-angiogenic properties of PEDF. The review evaluated its effects on retinal health, its dysregulation in ocular disorders, and its therapeutic application in preclinical models. Advances in drug delivery, including gene therapy, were also examined. Results: PEDF, initially identified for promoting neuronal differentiation, is also a potent endogenous angiogenesis inhibitor. Strong anti-angiogenic and neuroprotective effects are observed in preclinical studies. It has pro-apoptotic and antiproliferative effects on endothelial cells thereby reducing neovascularization. Although promising, clinical development is limited with only a single conducted phase I clinical trial for macular neovascularization. Development of PEDF-derived peptides enhances potency and specificity, and emerging gene therapy approaches offer sustained PEDF expression for long-term treatment. However, questions regarding dosage, durability, and efficacy remain, particularly in large animal models. Conclusions: PEDF shows significant therapeutic potential in preclinical models of retinal degeneration and vascular disorders. Despite inconclusive evidence on PEDF downregulation as a primary disease driver, many studies highlight its therapeutic benefits and favorable safety profile. Advances in gene therapy could enable long-acting PEDF-based treatments, but further research is needed to optimize dosage and durability, potentially leading to clinical trials and expanding treatment options for retinal disorders.