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Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration.

Publication ,  Journal Article
Malek, G; Johnson, LV; Mace, BE; Saloupis, P; Schmechel, DE; Rickman, DW; Toth, CA; Sullivan, PM; Bowes Rickman, C
Published in: Proc Natl Acad Sci U S A
August 16, 2005

Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dependent pathologies of differential severity. ApoE4 mice are the most severely affected. They develop a constellation of changes that mimic the pathology associated with human AMD. These alterations include diffuse sub-retinal pigment epithelial deposits, drusenoid deposits, thickened Bruch's membrane, and atrophy, hypopigmentation, and hyperpigmentation of the retinal pigment epithelium. In extreme cases, apoE4 mice also develop marked choroidal neovascularization, a hallmark of exudative AMD. Neither age nor HF-C diet alone is sufficient to elicit these changes. We document choroidal neovascularization and other AMD-like ocular pathologies in an animal model that exploits known AMD risk factors. The model is additionally attractive because it is not complicated by invasive experimental intervention. Our findings in this model implicate the human apoE E4 allele as a susceptibility gene for AMD and support the hypothesis that common pathogenic mechanisms may underlie AMD and Alzheimer's disease.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 16, 2005

Volume

102

Issue

33

Start / End Page

11900 / 11905

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Retinal Degeneration
  • Models, Biological
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice
  • Male
  • Humans
  • Female
  • Cholesterol
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Malek, G., Johnson, L. V., Mace, B. E., Saloupis, P., Schmechel, D. E., Rickman, D. W., … Bowes Rickman, C. (2005). Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A, 102(33), 11900–11905. https://doi.org/10.1073/pnas.0503015102
Malek, G., L. V. Johnson, B. E. Mace, P. Saloupis, D. E. Schmechel, D. W. Rickman, C. A. Toth, P. M. Sullivan, and C. Bowes Rickman. “Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration.Proc Natl Acad Sci U S A 102, no. 33 (August 16, 2005): 11900–905. https://doi.org/10.1073/pnas.0503015102.
Malek G, Johnson LV, Mace BE, Saloupis P, Schmechel DE, Rickman DW, et al. Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11900–5.
Malek, G., et al. “Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration.Proc Natl Acad Sci U S A, vol. 102, no. 33, Aug. 2005, pp. 11900–05. Pubmed, doi:10.1073/pnas.0503015102.
Malek G, Johnson LV, Mace BE, Saloupis P, Schmechel DE, Rickman DW, Toth CA, Sullivan PM, Bowes Rickman C. Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11900–11905.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 16, 2005

Volume

102

Issue

33

Start / End Page

11900 / 11905

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Retinal Degeneration
  • Models, Biological
  • Microscopy, Electron
  • Mice, Transgenic
  • Mice
  • Male
  • Humans
  • Female
  • Cholesterol