Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration

Nat Commun. 2022 Jan 18;13(1):374. doi: 10.1038/s41467-021-27935-9.


Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Chloride Channels / deficiency
  • Chloride Channels / genetics*
  • Disease Models, Animal
  • Fundus Oculi
  • Homeostasis
  • Lipid Metabolism
  • Macular Degeneration / diagnostic imaging
  • Macular Degeneration / genetics*
  • Macular Degeneration / physiopathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics*
  • Organ Specificity / genetics
  • Retinal Drusen / complications
  • Retinal Drusen / diagnostic imaging
  • Retinal Drusen / pathology
  • Retinal Pigment Epithelium / diagnostic imaging
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / physiopathology
  • Retinal Pigment Epithelium / ultrastructure
  • Risk Factors
  • Transcription, Genetic
  • Vision, Ocular / physiology


  • CLIC protein, mouse
  • Chloride Channels
  • Mitochondrial Proteins