May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Retinal Gene Expression Alterations in Age Related Macular Degeneration
Author Affiliations & Notes
  • I. Chowers
    Ophthalmology, Hebrew Univ–Hadasah Med Ctr, Jerusalem, Israel
  • D. Liu
    Biostatistics, Johns Hopkins University, Baltimore, MD
  • R.H. Farkas
    Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Inst, Johns Hopkins University School of Medicine, Baltimore, MD
  • T.L. Gunatilaka
    Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Inst, Johns Hopkins University School of Medicine, Baltimore, MD
  • C. Wang
    Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Inst, Johns Hopkins University School of Medicine, Baltimore, MD
  • A.S. Hackam
    Bascom Palmer Eye Inst, University of Miami School of Medicine, Miami, FL
  • M. Kageyama
    Santen Pharmaceuticals, Ikoma, Japan
  • P.A. Campochiaro
    Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Inst, Johns Hopkins University School of Medicine, Baltimore, MD
  • G. Parmigiani
    Biostatistics, Johns Hopkins University, Baltimore, MD
  • D.J. Zack
    Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Eye Inst, Johns Hopkins University School of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships  I. Chowers, Santen Pharmaceutical Co., LTD P; D. Liu, None; R.H. Farkas, Santen Pharmaceuticals Co, LTD F; T.L. Gunatilaka, Santen Pharmaceuticals Co, LTD F; C. Wang, Santen Pharmaceuticals Co, LTD F; A.S. Hackam, Santen Pharmaceuticals Co, LTD F; M. Kageyama, Santen Pharmaceuticals Co, LTD E; P.A. Campochiaro, None; G. Parmigiani, None; D.J. Zack, Santen Pharmaceuticals Co, LTD P.
  • Footnotes
    Support  Santen Pharmaceutical Co., LTD
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1151. doi:
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      I. Chowers, D. Liu, R.H. Farkas, T.L. Gunatilaka, C. Wang, A.S. Hackam, M. Kageyama, P.A. Campochiaro, G. Parmigiani, D.J. Zack; Retinal Gene Expression Alterations in Age Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1151.

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

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Abstract

Abstract: : Purpose: In age related macular degeneration (AMD) the neuroretina overlying affected retinal pigmented epithelium shows progressive degenerative changes. We aimed to identify retinal gene expression alterations associated with AMD in order to obtain insight into the molecular pathways underlying this process. Methods: Gene expression patterns were characterized in 12 retinas from 6 donors that had AMD, and in 33 retinas from 19 unaffected donors using a human retina custom cDNA microarray. A custom statistical model was designed to quantify the effects of age, gender, AMD, and their interactions on retinal gene expression. Quantitative real–time RT–PCR (QPCR) was applied to validate microarray results on the same set of eyes used for array experiments as well as on five AMD retinas not tested by the arrays. Results:Overall, in AMD retinas, approximately 8.9% of observed gene expression variation was attributed to AMD, while 5.1% and 4.3% of expression variation was attributed to age and gender, respectively. Multiple genes showed disease–associated expression. For example, there were 233 genes (false discovery rate = 18.7%), and 126 genes (false discovery rate = 28.5%) that showed at least two–fold mean expression level difference between non–neovascular AMD and unaffected eyes, and between neovascular AMD and unaffected eyes, respectively. As a group, photoreceptor enriched genes had an AMD associated expression pattern. QPCR results corroborated the microarray data for 5 of the eight genes tested (correlation coefficient = 0.59). Conclusions: Significant retinal gene expression alterations in multiple genes are associated with AMD, although many of the same genes also manifest substantial expression variations among patients. These results underscore the complexity of the molecular processes associated with AMD, and suggest that AMD is not homogenous in terms of the molecular events associated with the disease process in the neuroretina. Some of the genes identified in this research are candidates for further studies aimed to elucidate their potential role in AMD pathogenesis.

Keywords: age-related macular degeneration • gene microarray • gene/expression 
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