Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

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 r...

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Bibliographic Details
Published in:Progress in retinal and eye research 2015-03, Vol.45, p.1-29
Main Authors: Whitmore, S. Scott, Sohn, Elliott H., Chirco, Kathleen R., Drack, Arlene V., Stone, Edwin M., Tucker, Budd A., Mullins, Robert F.
Format: Article
Language:English
Subjects:
Age-related macular degeneration
Aging - physiology
Bruch Membrane - blood supply
Choriocapillaris
Choroid - blood supply
Choroidmacula
Complement Activation - physiology
Complement system
Complement System Proteins - genetics
Complement System Proteins - physiology
Endothelial cells
Humans
Macular Degeneration - genetics
Macular Degeneration - immunology
Macular Degeneration - physiopathology
Pathophysiology
Retinal Pigment Epithelium - blood supply
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Summary: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.
ISSN:1350-9462
1873-1635
DOI:10.1016/j.preteyeres.2014.11.005