May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Advanced Lipoxidation Endproducts (ALEs) and RPE Dysfunction – A Link to Age–Related Macular Degeneration (AMD)?
Author Affiliations & Notes
  • J.B. O'Neill
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • J.V. Glenn
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • T.E. DeGooyer
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • X. Zhang
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • M.B. Boulton
    School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom
  • K. Uchida
    Department of Food & Biodynamics, Nagoya University, Furo–cho,Chikusa–ku,Nagoya, Japan
  • U. Chakravarthy
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • R.E. Hogg
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • T. Curtis
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • A.W. Stitt
    Centre for Vision Science and Vascular Biology, Queen's University, Belfast, United Kingdom
  • Footnotes
    Commercial Relationships  J.B. O'Neill, None; J.V. Glenn, None; T.E. DeGooyer, None; X. Zhang, None; M.B. Boulton, None; K. Uchida, None; U. Chakravarthy, None; R.E. Hogg, None; T. Curtis, None; A.W. Stitt, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 2874. doi:
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      J.B. O'Neill, J.V. Glenn, T.E. DeGooyer, X. Zhang, M.B. Boulton, K. Uchida, U. Chakravarthy, R.E. Hogg, T. Curtis, A.W. Stitt; Advanced Lipoxidation Endproducts (ALEs) and RPE Dysfunction – A Link to Age–Related Macular Degeneration (AMD)? . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2874.

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

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Abstract

Purpose: : Advanced lipoxidation endproducts (ALEs) may play a causative role in disease, accumulating as heterogeneous chemical adducts on proteins during aging and at an accelerated rate in smokers. ALE modifications can alter protein structure and function although their pathogenic role in the retina is largely unknown. The aldehyde acrolein is formed during cellular oxidative stress and can bind to ε–amino group of lysine to form the ALE, acrolein–lysine adduct (FDP–lysine). In the present study we have evaluated presence of FDP–lysine (a defined ALE) in AMD patients and tested the effects of this protein–modification on retinal pigment epithelium (RPE) function.

Methods: : FDP–lysine immunoreactivity was investigated in sera from a small cohort of patients with wet AMD and age/sex matched controls (n=20/group) using competitive ELISAs. FDP–lysine in the retina was also immunolocalised in post–mortem eyes from AMD patients. In a parallel in vitro study, confluent, quiescent RPE (ARPE–19) were exposed to FDP–lysine (10, 25 & 50 µM) for 7 days and assessed for apoptotic death by changes in annexin V or JC–1 under flow cytometric analysis. Alterations in antioxidant mRNAs were examined by real time RT–PCR and activation of transcriptional activity of NFΚB was quantified.

Results: : Serological data demonstrated significantly elevated levels of ALE in patients with AMD (P<0.005). Retinae from AMD patients also had elevated FDP–lysine–immunoreactivity compared to age–matched controls and this was localised to photoreceptor outer–segments, RPE, Bruch’s membrane and choroid. FDP–lysine–treated RPE did not show any evidence of apoptotic cell death after 7 days of treatment post confluency. Relative antioxidant gene expression in ARPE–19 was significantly reduced after FDP–lysine exposure. In response to increased FDP–lysine concentrations, NFΚB transcriptional activity was noticeably reduced in comparison to control (P<0.001).

Conclusions: : Data suggests that levels of FDP–lysine are increased in serum and retina from patients with AMD. This ALE may have an important pathogenic role in outer retinal ageing by altering antioxidant defence mechanisms in RPE.

Keywords: retinal pigment epithelium • immunohistochemistry • retina 
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