In a new study, researchers have discovered a method that may improve the current treatment for choroidal neovascularization (CNV), an aggressive form of age-related macular degeneration (AMD), the leading cause of blindness in the elderly.
The research was led by Baylor College of Medicine and Houston Methodist.
Anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment for CNV.
However, up to one-fourth of all treated patients are unresponsive to this treatment and about one-third of the responders become resistant to it after repeated administration over time.
In the study, the researchers found that combining apolipoprotein A-I binding protein (AIBP) with anti-VEGF overcomes anti-VEGF resistance and effectively suppresses CNV.
The findings open the possibility of reducing anti-VEGF resistance in patients in the future.
Previously, the team had found that macrophages may play a role in anti-VEGF resistance and that increased cholesterol accumulation in macrophages may promote CNV.
Such cholesterol accumulation also has been associated with the formation of abnormal new blood vessels invading the retina.
These vessels leak, which promotes inflammation and rapid photoreceptor (light-detecting cells) damage.
The researchers developed a model of anti-VEGF resistance and tested the effect of AIBP and anti-VEGF in disease progression in this mouse model.
They found the method worked well on the oldest group of mice, which was about 18 months old or the equivalent of senior people.
This study also has increased the understanding of the mechanism underlying anti-VEG resistance.
The team says that the beneficial effect of AIBP is likely due to both its ability to enhance cholesterol removal from macrophages and its anti-inflammatory function.
These findings encourage them to test the combination therapy of AIBP and anti-VEGF in clinical trials to determine whether it can help patients with the condition.
The projected number of people with age-related macular degeneration is 196 million in 2020 and 288 million in 2040. There is great interest in novel therapies for this devastating condition.
One author of the study is Dr. Yingbin Fu, an associate professor and Sarah Campbell Blaffer Endowed Chair of Ophthalmology at Baylor.
The study is published in the journal Communications Biology.
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