title: 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.
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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Smith Building, room 3015, 21287, Baltimore, MD, USA, kebrahi2@jhmi.edu.
authors.forename: Katayoon B
authors.initials: KB
authors.lastname: Ebrahimi
authors.forename: Natalia
authors.initials: N
authors.lastname: Fijalkowski
authors.forename: Marisol
authors.initials: M
authors.lastname: Cano
authors.forename: James T
authors.initials: JT
authors.lastname: Handa
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D001768:Blister / Q000276:immunology / Q000378:metabolism; D016570:Bruch Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018957:CD59 Antigens / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D055354:Exosomes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008268:Macular Degeneration / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051916:Membrane Cofactor Protein / Q000276:immunology* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C497857:CD46 protein, human; D018957:CD59 Antigens; D008077:Lipoproteins, LDL; D051916:Membrane Cofactor Protein; C099252:oxidized low density lipoprotein; C051590:CD59 protein, human; D003165:Complement System Proteins