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Pigment epithelium-derived factor (PEDF), encoded by the SERPINF1 gene, is a multifunctional secreted glycoprotein that serves as a critical regulator of the corneal limbal stem cell (LSC) niche. Although it is a member of the serpin superfamily, it lacks protease inhibitory activity and instead functions as one of the body's most potent anti-angiogenic and neurotrophic factors. In the ocular environment, PEDF-responsive pathways are essential for preserving the regenerative capacity of LSCs and maintaining the transparency of the cornea by preventing pathological blood vessel encroachment. PEDF exerts its biological effects by binding to specific receptors, most notably the phospholipase-linked PEDF-R (PNPLA2) and the Wnt-pathway co-receptor LRP6. Dysregulation of these pathways is a hallmark of limbal stem cell deficiency (LSCD) and various retinal degenerative diseases. Therapeutic strategies currently under investigation include the use of recombinant PEDF, synthetic PEDF-derived peptides, and gene therapy to restore ocular surface homeostasis and promote corneal wound healing. (Sources: UniProt P36955; PubMed: 23554555, 28205514).
PEDF binds to the PEDF-R (PNPLA2) receptor to activate phospholipase activity and interacts with the Wnt co-receptor LRP6 to modulate downstream signaling pathways, thereby maintaining the stemness and quiescence of limbal stem cells while antagonizing VEGF-mediated angiogenesis.
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