Altered cholesterol homeostasis in aged macrophages linked to neovascular macular degeneration

Abstract

Abnormal lipid metabolism has been linked to age-related macular degeneration (AMD); choroidal neovascularization in late AMD commonly causes blindness. Sene et al. (2013) now demonstrate that in aged macrophages decreased ABCA1 expression, regulated by liver X receptor and miR-33, impairs export of intracellular cholesterol, which promotes neovascular AMD.

Figure 1

[LS1]ABCA1 mediated cholesterol efflux influences choroidal neovascularization A: a schematic drawing of a human eye illustrates cholesterol containing drusen (yellow spots) and choroidal neovascularization (CNV) in the macula. B: Aging induces increased levels of miR-33, leading to decreased expression of cholesterol transporter ABCA1. Lack of ABCA1 results in impaired cholesterol efflux from macrophages, leading to alternative activation of macrophages from the classic M1 phenotype to the pro-angiogenic M2 phenotype, and thereby promotes laser-induced CNV formation. Activation of liver X receptor (LXR), a nuclear transcription factor, or inhibition of miR-33 both lead to increased ABCA1 and protection against CNV.