Excess cholesterol in macrophages within ocular blood vessels may help trigger neovascular, or "wet," age-related macular degeneration (AMD), a laboratory study suggested.
A series of experiments in mice showed that cholesterol levels in macrophages from older mice were higher than in younger animals, apparently because of impairments in the ABCA1 cholesterol efflux mechanism, according to Rajendra Apte, MD, PhD, of Washington University in St. Louis, and colleagues.
Topical as well as systemic treatment of older mice with a liver X receptor (LXR) agonist known as T0-901317, which boosts cholesterol efflux from cells, reduced the degree of choroidal neovascularization in a laser-induced model of the human disease, the researchers also reported in the April 2 issue of Cell Metabolism.
Apte and colleagues also confirmed in lab studies that human peripheral blood mononuclear cells show progressive ABCA1 impairment and cholesterol buildup with age.
However, despite headlines in consumer media suggesting that people with AMD could benefit immediately from anti-cholesterol medications, Apte and colleagues did not test whether the LXR agonist could prevent spontaneous neovascularization in mice, let alone humans.
Nor are there any LXR agonists approved for human use, although at least one has progressed as far as phase I clinical testing. Moreover, the study did not address "dry" AMD, the much more common but less severe form of AMD.
Nevertheless, Apte and colleagues argued that the results point to a new approach to treating wet AMD.
"Therapeutic intervention prior to the development of advanced disease with effective agents that upregulate macrophage cholesterol efflux in the eye might prevent progression and can be used as prophylaxis against the development of choroidal neovascularization and its blinding complications," they wrote.
LXR agonists have previously been suggested as treatments for Alzheimer's disease, glioblastoma, hypercholesterolemia, atherosclerosis, thrombosis, and a variety of other disorders.
John Gever
Senior Editor
John Gever, Senior Editor, has covered biomedicine and medical technology for 30 years. He holds a B.S. from the University of Michigan and an M.S. from Boston University. Now based in Pittsburgh, he is the daily assignment editor for MedPage Today as well as general factotum on the reporting side. Go Pirates/Penguins/Steelers!
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