Oxidized low-density-lipoprotein-induced injury in retinal pigment epithelium alters expression of the membrane complement regulatory factors CD46 and CD59 through exosomal and apoptotic bleb release

Adv Exp Med Biol. 2014;801:259-65. doi: 10.1007/978-1-4614-3209-8_33.

Abstract

Genetic and immunohistochemical studies have identified the alternative complement pathway as an important component of age-related macular degeneration (AMD). The objective of this chapter is to review the impact of complement regulators on complement activation in the macula as it relates to AMD. Our laboratory and other investigators have identified CD46 and CD59 as important retinal pigment epithelium (RPE) cell membrane complement regulators, which are decreased in AMD. Using oxidized low-density lipoproteins (oxLDLs), which are found in Bruch's membrane in AMD, we found that CD46 and CD59 were decreased in RPE cells in part, by their release in exosomes and apoptotic particles. The release of complement regulators could potentially impair complement regulation on RPE cells and contribute to lesion formation in the outer retina and Bruch's membrane during the development of AMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Blister / immunology
  • Blister / metabolism
  • Bruch Membrane / immunology
  • Bruch Membrane / metabolism
  • Bruch Membrane / pathology
  • CD59 Antigens / immunology*
  • CD59 Antigens / metabolism
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Exosomes / immunology
  • Exosomes / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism*
  • Macular Degeneration / immunology*
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Membrane Cofactor Protein / immunology*
  • Membrane Cofactor Protein / metabolism
  • Retinal Pigment Epithelium / immunology*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology

Substances

  • CD46 protein, human
  • CD59 Antigens
  • Lipoproteins, LDL
  • Membrane Cofactor Protein
  • oxidized low density lipoprotein
  • CD59 protein, human
  • Complement System Proteins