L009 peptide as a novel antiangiogenic agent for corneal neovascularization via regulation of the TNFSF15-VEGF axis.

Corneal neovascularization (CNV) is a leading cause of vision impairment, with existing therapeutic options offering limited efficacy. This study presents L009, a novel antiangiogenic agent derived from the Kringle 5 domain of human plasminogen, specifically a heptapeptide, designed to treat CNV. In preclinical models, L009 demonstrated substantial efficacy by markedly inhibiting endothelial cell proliferation and migration, reducing vascular permeability, and maintaining ocular safety. Mechanistically, L009 exerts its effects by upregulating tumor necrosis factor superfamily member 15 (TNFSF15), downregulating vascular endothelial growth factor receptor 2 (VEGFR2), and increasing the expression of soluble VEGFR1. These actions restore vascular homeostasis and enhance vascular stability through the upregulation of the tight junction protein VE-cadherin. By specifically targeting the TNFSF15-VEGF axis, L009 offers a distinctive therapeutic approach, differentiating it from conventional anti-VEGF therapies. Its dual action of anti-angiogenesis and promotion of vascular stability highlights its potential as a next-generation treatment for CNV. Further investigation into its long-term efficacy and potential for synergy with existing therapies is warranted.