Regulation of ABCA1 by miR-33 and miR-34a in the Aging Eye

Adv Exp Med Biol. 2023:1415:55-59. doi: 10.1007/978-3-031-27681-1_9.

Abstract

Many age-related diseases, including age-related macular degeneration (AMD), go along with local lipid accumulation and dysregulated lipid metabolism. Several genes involved in lipid metabolism, including ATP-binding cassette transporter A1 (ABCA1), were associated with AMD through genome-wide association studies. Recent studies have shown that loss of ABCA1 in the retinal pigment epithelium (RPE) leads to lipid accumulation and RPE atrophy, a hallmark of AMD, and that antagonizing ABCA1-targeting microRNAs (miRNAs) attenuated pathological changes to the RPE or to macrophages. Here, we focus on two lipid metabolism-modulating miRNAs, miR-33 and miR-34a, which show increased expression in aging RPE cells, and on their potential to regulate ABCA1 levels, cholesterol efflux, and lipid accumulation in AMD pathogenesis.

Keywords: ABCA1; AMD; Cholesterol; HDL; LXR; Lipid accumulation; Lipids; RPE; Reverse cholesterol transport; miRNA.

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • Aging / genetics
  • Cholesterol / metabolism
  • Genome-Wide Association Study
  • Humans
  • Macular Degeneration* / genetics
  • Macular Degeneration* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Retinal Pigment Epithelium / metabolism

Substances

  • Cholesterol
  • MicroRNAs
  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1