Lysophospholipid Signaling Molecules in Fundus Neovascular Diseases

Fundus neovascular diseases (FNDs) are vision-threatening ocular disorders featuring pathological neovascularization and pose a major global threat to vision health. Their pathogenesis is heterogeneous, involving multiple factors and pathways. Current clinical pharmacotherapies only target a limited range of molecular pathways via narrow mechanisms, leading to frequent suboptimal responses and disease recurrence, which restricts further therapeutic improvement for FNDs. Recent studies demonstrate that lysophospholipid signaling molecules selectively activate multiple cell-surface receptors, including G protein-coupled receptors, triggering multilayered downstream signaling cascades that govern neovascular initiation and progression. Aberrant activation of this endogenous signaling axis may underpin the limited efficacy of existing anti-angiogenic therapies, and its roles in pathological neovascularization have attracted intensive research attention. This review addresses three representative lysophospholipid mediators: lysophosphatidic acid, lysophosphatidylcholine, and sphingosine-1-phosphate. We systematically summarize their metabolic routes, receptor binding profiles, downstream signaling networks, and pro-angiogenic mechanisms. We also discuss the current research status and translational potential of targeting lysophospholipid axes as innovative therapies, aiming to provide theoretical and translational evidence for developing precise pathway-directed interventions.