Research progress on chronic inflammation in wet age-related macular degeneration

Age-related macular degeneration (AMD) is a major cause of irreversible vision loss among elderly populations in developed countries. Wet AMD (wAMD), characterized by choroidal neovascularization and acute vision decline, has increasingly been understood through a pathological framework that emphasizes the interplay between chronic inflammation and angiogenesis, moving beyond earlier theories focused solely on vascular dysregulation. The inflammatory regulatory network in wAMD involves multiple pathways, including aberrant activation of the complement system, NLRP3 inflammasome-mediated pyroptosis, and dysfunctional microglial polarization. These inflammatory signaling pathways extensively crosstalk with the VEGF pathway, collectively exacerbating vascular leakage and photoreceptor cell damage. Emerging biomarkers, such as CXCL10/IP-10 and CCL2/MCP-1, along with novel therapeutic strategies like complement inhibition and CRISPR-based gene editing, hold promise for improving diagnostic accuracy and treatment precision in wAMD. In the era of multi-omics technologies and personalized medicine, combined anti-VEGF therapy with immunomodulatory and metabolic interventions is becoming a promising direction to overcome treatment resistance in wAMD. This review systematically summarizes the multi-level regulatory mechanisms of chronic inflammation in wAMD and discusses its clinical translation prospects, aiming to provide a theoretical foundation for precision medicine in wAMD management.