Artistic representation of cholesterol in a blood vessel. Credit: Tlecoatl Zyanya

A team of international researchers found artificially increasing levels of apolipoprotein M (ApoM), a natural protein involved in cholesterol metabolism, improved retinal pigment epithelium (RPE) function in mice with age-related macular degeneration (AMD).

Writing in Nature Communications, researchers said they set out to investigate whether reduced ApoM levels, which fall with age, could be involved in the dysfunctional cholesterol metabolism at the root of diseases including AMD and cardiovascular disease (CVD). They discovered that patients with AMD had significantly reduced circulating ApoM, rendering retina and heart muscle cells unable to fully metabolise cholesterol deposits and accumulating inflammation-causing lipids.

When plasma from ApoM-overexpressing mice was administered to mice with knockouts in key genes in cholesterol metabolism, the development of AMD-like phenotypes was attenuated. In contrast, plasma from ApoM-knockout mice had no such effect, said researchers.

“We demonstrated that several pathogenic features observed in murine models of dry AMD, such as RPE and rod photoreceptor dysfunction and RPE lipid accumulation, are improved by ApoM.” The researchers also suggested a novel role for the lipocalin ApoM in addressing RPE lipotoxicity, as seen in early dry AMD.