Version 1
: Received: 12 January 2024 / Approved: 15 January 2024 / Online: 15 January 2024 (07:10:37 CET)
Version 2
: Received: 31 January 2024 / Approved: 1 February 2024 / Online: 1 February 2024 (11:24:15 CET)
Fu, Y.; Zhang, Z.; Webster, K.A.; Paulus, Y.M. Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization. Biomolecules2024, 14, 252.
Fu, Y.; Zhang, Z.; Webster, K.A.; Paulus, Y.M. Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization. Biomolecules 2024, 14, 252.
Fu, Y.; Zhang, Z.; Webster, K.A.; Paulus, Y.M. Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization. Biomolecules2024, 14, 252.
Fu, Y.; Zhang, Z.; Webster, K.A.; Paulus, Y.M. Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization. Biomolecules 2024, 14, 252.
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 declined 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.
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