Publication Date
2-21-2024
Journal
Biomolecules
DOI
10.3390/biom14030252
PMID
38540673
PMCID
PMC10968528
PubMedCentral® Posted Date
2-21-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Humans, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Macular Degeneration, Choroidal Neovascularization, Vascular Endothelial Growth Factors, Cholesterol, choroidal neovascularization, CNV, anti-VEGF resistance, neovascular age-related macular degeneration, AMD, arteriolar CNV, anti-VEGF therapies, capillary CNV, AIBP, apoA-I
Abstract
Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.