title: Complement activation and choriocapillaris loss in early AMD: implications for pathophysiology and therapy.
abstract: Age-related macular degeneration (AMD) is a common and devastating disease that can result in severe visual dysfunction. Over the last decade, great progress has been made in identifying genetic variants that contribute to AMD, many of which lie in genes involved in the complement cascade. In this review we discuss the significance of complement activation in AMD, particularly with respect to the formation of the membrane attack complex in the aging choriocapillaris. We review the clinical, histological and biochemical data that indicate that vascular loss in the choroid occurs very early in the pathogenesis of AMD, and discuss the potential impact of vascular dropout on the retinal pigment epithelium, Bruch's membrane and the photoreceptor cells. Finally, we present a hypothesis for the pathogenesis of early AMD and consider the implications of this model on the development of new therapies.
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: S Scott
authors.initials: SS
authors.lastname: Whitmore
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sohn
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Chirco
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Arlene V
authors.initials: AV
authors.lastname: Drack
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, The University of Iowa, United States; Department of Ophthalmology and Visual Sciences, The University of Iowa, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
mesh_terms: D000375:Aging / Q000502:physiology; D016570:Bruch Membrane / Q000098:blood supply; D002829:Choroid / Q000098:blood supply*; D003167:Complement Activation / Q000502:physiology*; D003165:Complement System Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000098:blood supply
chemical_list: D003165:Complement System Proteins
keywords: Age-related macular degeneration; Choriocapillaris; Choroidmacula; Complement system; Endothelial cells; Pathophysiology