March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Properdin and Malondialdehyde (MDA) effects on the APOE4 mouse model of Age-Related Macula Degeneration (AMD)
Author Affiliations & Notes
  • Una L. Kelly
    Ophthalmology,
    Duke University Medical Center, Durham, North Carolina
  • Marybeth Groelle
    Ophthalmology,
    Duke University Medical Center, Durham, North Carolina
  • Jindong Ding
    Ophthalmology,
    Duke University Medical Center, Durham, North Carolina
  • Wen-Chao Song
    School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
  • Catherine Bowes Rickman
    Ophthalmology and Cell Biology,
    Duke University Medical Center, Durham, North Carolina
  • Footnotes
    Commercial Relationships  Una L. Kelly, None; Marybeth Groelle, None; Jindong Ding, None; Wen-Chao Song, None; Catherine Bowes Rickman, None
  • Footnotes
    Support  NIH Grant EY019038, P30 EY005722, Research to Prevent Blindness, Inc., Ruth and Milton Steinbach Fund, Macular Vision Research Foundation
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6466. doi:https://doi.org/
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      Una L. Kelly, Marybeth Groelle, Jindong Ding, Wen-Chao Song, Catherine Bowes Rickman; Properdin and Malondialdehyde (MDA) effects on the APOE4 mouse model of Age-Related Macula Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2012;53(14):6466. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Aged human apolipoprotein E4 targeted replacement (APOE4) mice on a high fat, cholesterol-enriched (HFC) diet are a recognized mouse model of AMD. This study was designed to further interrogate aspects of the roles of each of the essential components of the model on the subsequent development of an AMD-like phenotype. Specifically, we examined the effect of the HFC diet on properdin levels and studied the effects of aging and expression of human APOE4 on plasma levels of MDA-adducted proteins.

Methods: : Two sets of mice were used for this study: a) 70 week old mice fed a HFC diet for 16 weeks. Western blot analysis was used to measure plasma properdin levels throughout the course of exposure to the HFC diet (blood was taken at day 0 and 1, and weeks 1, 4, 8 and 16) and C3a desArg was measured by ELISA and b) 4 strains of mice(cfh-/-, sCrry, APOE4 and APOE4/sCrry) all on a C57/Bl6 background and normal diet had blood taken at 6, 30, 57, and 72 weeks of age. Western blot analysis of these plasma samples using an anti-MDA antibody was performed.

Results: : Plasma properdin levels rose in the plasma in mice by 1 week on the HFC diet, reaching a maximum concentration by 8 weeks and remaining at this level for 16 weeks. C3a desArg levels also increased with the HFC diet. On immunoblots of plasma obtained from APOE4 mouse strains an additional band was detected by the anti-MDA antibody and the concentration of this band and another dominant band were higher in these mice than in the other strains. We are currently investigating the identity of these bands. All of the mice showed an age-related increase in levels of detected MDA.

Conclusions: : Increased levels of plasma properdin, which stabilizes the C3 convertase, C3bBb, and thereby activates complement, could be a contributing factor to the increased complement activation (increased C3a desArg) detected in the APOE4 mouse model. Furthermore, the increased MDA-adducted proteins in the plasma of the aged APOE4 mice suggest that these mice are less able to tolerate oxidative stress associated with aging. These findings further support a role for complement activation and oxidative stress in the development of the phenotype seen in this AMD mouse model as has been proposed for the pathogenesis of AMD.

Keywords: age-related macular degeneration • immunomodulation/immunoregulation • oxidation/oxidative or free radical damage 
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