April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Relation of RPE Phagocytosis and Oxidative Stress: Molecular Mechanisms
Author Affiliations & Notes
  • S. C. Finnemann
    Biological Sciences, Fordham University, Bronx, New York
  • C.-C. Yu
    Biological Sciences, Fordham University, Bronx, New York
  • C. Scelfo
    Biological Sciences, Fordham University, Bronx, New York
  • Footnotes
    Commercial Relationships  S.C. Finnemann, None; C.-C. Yu, None; C. Scelfo, None.
  • Footnotes
    Support  NIH grant EY13295, California Table Grape Commission
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3523. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S. C. Finnemann, C.-C. Yu, C. Scelfo; Relation of RPE Phagocytosis and Oxidative Stress: Molecular Mechanisms. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3523.

      Download citation file:

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

  • Supplements

Purpose: : Cumulative oxidative damage of the retinal pigment epithelium (RPE) layer of the retina causes formation of pro-oxidant lipofuscin and contributes to RPE dysfunction and atrophy in dry AMD. We previously showed that oxidative processes secondary to loss of the diurnal rhythm of photoreceptor outer segment phagocytosis cause age-related loss of photoreceptor function (but not viability) and RPE lipofuscin accumulation in β5 integrin knockout mice. Moreover, we demonstrated that dietary supplementation with antioxidants is sufficient to prevent vision loss with age in these mice. Our parallel experiments exploring RPE cells in culture further suggest that minor, by themselves innocuous, delay in lysosomal digestion of engulfed outer segment fragments and inefficient mitochondrial metabolism synergistically impair the RPE’s phagocytic activity towards outer segments. This study aims to identify specific molecules functionally related to phagocytosis and to energy metabolism that are modified by physiologically relevant oxidative stress in the RPE in culture and in the eye.

Methods: : We raised age- and strain-matched cohorts of wild-type and β5 knockout mice, divided cohorts into groups receiving anti-oxidant supplementation and groups receiving placebo. We collected neural retina and eyecup samples from mice sacrificed at different ages. We compared quantity and quality of oxidative modifications of proteins known to be involved in the diurnal phagocytic activity of the RPE with age among tissue samples. In complementary experiments, we performed the same measurements on samples obtained from RPE cells in culture comparing cells fed or not with isolated photoreceptor outer segment fragments with either intact or impaired mitochondrial ATP synthesis.

Results: : Our experiments demonstrated that specific components of the RPE phagocytic machinery itself acquire oxidative modifications as a function of age and in response to chronic oxidative stress. RPE cells of β5 integrin knockout mice fed with antioxidant-enriched diet that is effective in preventing vision loss with age possessed a phagocytic machinery with significantly lower levels of modifications compared to RPE cells of β5 integrin knockout mice on placebo diet.

Conclusions: : Chronic, low levels of oxidative stress and gradual decline in cellular functions with age synergize to impair RPE activities that are likely directly relevant for the development of age-related human retinal disease including AMD. Our results are the first to demonstrate that (and via which protein targets) oxidative stress with age impairs the molecular machinery for RPE phagocytosis, a critical function of RPE cells in support of photoreceptor functions.

Keywords: retinal pigment epithelium • oxidation/oxidative or free radical damage • mitochondria 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.