Cited by 182Retinal Development and DisordersRetinal Diseases and TreatmentsLysosomal Storage Disorders Research

Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration

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Karan, G., Lillo, C., Yang, Z., Cameron, D. J., Locke, K. G., Zhao, Y., Thirumalaichary, S., Li, C. +4 more·2005·Proceedings of the National Academy of Sciences

Abstract

Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness.

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Crossref · 10.1073/pnas.0407698102

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  • Defective OS phagosome motility and degradation has been found in a mouse model of Stargardt macular degeneration (type 3), leading to phagosome accumulation, RPE pathogenesis, and photoreceptor cell death.

    “In a second example, defective OS phagosome motility and degradation has been found in a mouse model of Stargardt macular degeneration (type 3) (Esteve-Rudd et al., 2018), leading to phagosome accumulation, RPE pathogenesis, and photoreceptor cell death (Karan et al., 2005).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Karan et al., 2005

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Authors
Karan, G., Lillo, C., Yang, Z., Cameron, D. J., Locke, K. G., Zhao, Y., Thirumalaichary, S., Li, C., Birch, D. G., Vollmer-Snarr, H. R., Williams, D. S., & Zhang, K.
Affiliations
Brigham Young University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2005-03-04
Volume
102
Issue
11
Pages
4164-4169
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2043251036
Cited by
182
References
27
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 10 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 13
FWCI
4.79
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Health Assistance Foundation
  • Ronald McDonald House Charities
  • Karl Kirchgessner Foundation
  • Research to Prevent Blindness
  • Brigham Young University
  • Deutsches Krebsforschungszentrum
  • National Institutes of Health (5p30ey012598-05, M01-RR00064)
  • National Eye Institute (R01EY014448, R01EY05235, R01EY13408, P30-EY012598, R01EY013408, P30-EY12598, R01EY014428, R01EY14428, R01EY14448, R01EY007042, R01EY005235)
  • National Center for Research Resources (M01-RR 00064, M01RR000064)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
ELOVL4, macular degeneration, lipofuscin accumulation, retinal pigment epithelium atrophy, photoreceptor degeneration, transgenic mouse model, retinal electrophysiology, age-related macular degeneration
MeSH terms
Animals, Disease Models, Animal, Electrophysiology, Eye Proteins, Humans, Lipofuscin, Macular Degeneration, Membrane Proteins, Mice, Transgenic, Microscopy, Electron, Photoreceptor Cells, Retina, Mice

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