May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Differential Gene Expression between Macular and Equatorial Human RPE Cells in Response to Oxidative Stress
R. E. Ramirez; S. Zareparsi; H. Lin; F. Q. Liang; J. Cai; M. E. Boulton; A. Swaroop; B. F. Godley
Author Affiliations & Notes
  • R. E. Ramirez
    Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas
  • S. Zareparsi
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
  • H. Lin
    Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas
  • F. Q. Liang
    Retina Foundation of the Southwest, UT Southwestern Medical Center, Dallas, Texas
  • J. Cai
    Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas
  • M. E. Boulton
    Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas
  • A. Swaroop
    Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
  • B. F. Godley
    Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas
  • Footnotes
    Commercial Relationships R.E. Ramirez, None; S. Zareparsi, None; H. Lin, None; F.Q. Liang, None; J. Cai, None; M.E. Boulton, None; A. Swaroop, None; B.F. Godley, None.
  • Footnotes
    Support NIH Grant EY 12850
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2936. doi:
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      R. E. Ramirez, S. Zareparsi, H. Lin, F. Q. Liang, J. Cai, M. E. Boulton, A. Swaroop, B. F. Godley; Differential Gene Expression between Macular and Equatorial Human RPE Cells in Response to Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2936.

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Abstract

Purpose:: Current evidence strongly supports that oxidative stress contributes to RPE dysfunction and loss in AMD. Our previous data show that RPE cells from the macula have increased susceptibility to oxidative stress compared to peripheral RPE cells. In this study, we have investigated the molecular basis of this differential susceptibility of macular versus peripheral RPE cells to oxidative stress.

Methods:: RPE cells from macula and equatorial regions of human donor eyes of different ages were isolated and cultured. Primary RPE cultures were exposed to hydrogen peroxide (H2O2) at varying concentrations for 1 hour. Mitochondrial redox function was measured by the MTT assay and the gene expression profiles were obtained with high-density oligonucleotide microarrays (Affymetrix).

Results:: Our result confirm that the mitochondria of macular RPE cells are more sensitive to H2O2 in comparison to those of peripheral RPE cells. This susceptibility of macular RPE cells to H2O2 remained through multiple passages in cell culture and vulnerability to oxidative stress increases with age. The microarrays data showed that H2O2 treatment resulted in different gene expression profiles between macular and peripheral RPE cells (200 genes in macular RPE cells; 413 genes in peripheral RPE cells). Two interesting gene, one encodes a transcription factor (ATF3) which is responsible for cellular damage and apoptosis and the other encodes a G-protein regulator(RGS2) that is related to oxidative stress-associated neurodegenerative diseases such as Alzheimer's. Both genes were prominently expressed in macular RPE cells when exposed to oxidative stress. In addition, a similar trend was found with several genes related to p53-mediated cell-cycle arrest in response to DNA damage.

Conclusions:: Identification of specific genes from macular RPE cells with increasing susceptibility to oxidative stress may serve as novel therapeutic targets for AMD.

Keywords: oxidation/oxidative or free radical damage • retinal pigment epithelium • gene microarray 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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