Seminar Title: Combating drug resistance in age-related macular degeneration
Time: 3 p.m. via Zoom
Speaker Bio: Dr. Yingbin Fu is an associate professor of ophthalmology and Sarah Campbell Blaffer Endowed chair at Baylor College of Medicine, Houston, Texas.
Seminar Summary: Choroidal neovascularization (CNV), which accounts for 10-20 percent of AMD, is responsible for 80-90 percent of AMD-related blindness. Anti-VEGF therapies that target extracellular VEGF have revolutionized the treatment for CNV; however, it is estimated that up to 50 percent of patients have poor responses to this treatment. Different strategies have been tested to overcome this issue. However, no major breakthrough has been reported in combating anti-VEGF resistance. The mechanisms for anti-VEGF resistance are poorly understood. We explore the unique property of the apolipoprotein A-I (apoA-I) binding protein (AIBP) that enhances cholesterol efflux from endothelial cells and macrophages to thereby limit angiogenesis and inflammation to tackle anti-VEGF resistance in CNV. We show that laser-induced CNV in mice with increased age showed increased resistance to anti-VEGF treatment, which correlates with increased lipid accumulation in macrophages. The combination of AIBP/apoA-I and anti-VEGF treatment overcomes anti-VEGF resistance and effectively suppresses CNV. Furthermore, macrophage depletion in old mice restores CNV sensitivity to anti-VEGF treatment and blunts the synergistic effect of combination therapy. These results suggest that cholesterol-laden macrophages play a critical role in inducing anti-VEGF resistance in CNV. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.