Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models

J Ocul Pharmacol Ther. 2022 Jan-Feb;38(1):3-32. doi: 10.1089/jop.2021.0067. Epub 2021 Nov 17.

Abstract

Age-related macular degeneration (AMD) is a major leading cause of irreversible visual impairment in the world with limited therapeutic interventions. Histological, biochemical, genetic, and epidemiological studies strongly implicate dysregulated lipid metabolism in the retinal pigmented epithelium (RPE) in AMD pathobiology. However, effective therapies targeting lipid metabolism still need to be identified and developed for this blinding disease. To test lipid metabolism-targeting therapies, preclinical AMD mouse models are needed to establish therapeutic efficacy and the role of lipid metabolism in the development of AMD-like pathology. In this review, we provide a comprehensive overview of current AMD mouse models available to researchers that could be used to provide preclinical evidence supporting therapies targeting lipid metabolism for AMD. Based on previous studies of AMD mouse models, we discuss strategies to modulate lipid metabolism as well as examples of studies evaluating lipid-targeting therapeutics to restore lipid processing in the RPE. The use of AMD mouse models may lead to worthy lipid-targeting candidate therapies for clinical trials to prevent the blindness caused by AMD.

Keywords: age-related macular degeneration; complement; lipid metabolism; mouse models; retinal pigmented epithelium; therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Lipid Metabolism / physiology*
  • Macular Degeneration / genetics
  • Macular Degeneration / physiopathology*
  • Mice
  • Risk Factors