Article Text

other Versions

PDF
The oil spill in ageing Bruch membrane
  1. Christine A Curcio1,
  2. Mark Johnson2,
  3. Martin Rudolf3,4,
  4. Jiahn-Dar Huang5
  1. 1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, USA
  2. 2Biomedical Engineering Department, Northwestern University, Evanston, Illinois, USA
  3. 3Department of Ophthalmology, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
  4. 4University Eye Hospital Lübeck, Lübeck, Germany
  5. 5National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Professor Christine A Curcio, Department of Ophthalmology, EyeSight Foundation of Alabama Vision Science Laboratories Room 360, University of Alabama School of Medicine, Birmingham, AL 35294-0019, USA; curcio{at}uab.edu

Abstract

Ageing is the largest risk factor for age-related macular degeneration (AMD), and soft drusen and basal linear deposits are lipid-rich extracellular lesions specific to AMD. Oil red O binding neutral lipid represents a major age-related deposition in the Bruch membrane (BrM) and the first identified druse component. Decades after these seminal observations, a natural history of neutral lipid deposition has been articulated and a biochemical model proposed. Results obtained with multiple biochemical, histochemical, and ultrastructural methods, and supported indirectly by epidemiology, suggest that the RPE secretes apolipoprotein B (apoB)-lipoprotein particles of unusual composition into BrM, where they accumulate with age eventually forming a lipid wall, a precursor of basal linear deposit. The authors propose that constituents of these lesions interact with reactive oxygen species to form pro-inflammatory peroxidised lipids that elicit neovascularisation. Here, the authors summarise key evidence supporting both accumulation of BrM lipoproteins leading to lesion formation and lipoprotein production by the RPE. The authors update their model with genetic associations between AMD and genes historically associated with plasma HDL metabolism, and suggest future directions for research and therapeutic strategies based on an oil-spill analogy.

  • Age-related macular degeneration
  • ageing
  • retinal pigment epithelium
  • Bruch membrane
  • lipoproteins
  • apolipoprotein B
  • drusen
  • basal deposits
  • cholesterol
  • cholesteryl ester
  • degeneration
  • biochemistry
  • eye (tissue) banking
  • pathology
  • anatomy
  • retina
  • macula
  • neovascularisation

Statistics from Altmetric.com

Footnotes

  • Funding NIH grants EY06109 and EY014662, International Retinal Research Foundation, American Health Assistance Foundation, EyeSight Foundation of Alabama, Research to Prevent Blindness, Inc., Macula Vision Research Foundation, Roger Johnson Prize in Macular Degeneration Research, and Deutsche Forschungsgemeinschaft.

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.