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

Prog Retin Eye Res. 2015 Mar;45:1-29. doi: 10.1016/j.preteyeres.2014.11.005. Epub 2014 Dec 5.


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.

Keywords: Age-related macular degeneration; Choriocapillaris; Choroidmacula; Complement system; Endothelial cells; Pathophysiology.

Publication types

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

MeSH terms

  • Aging / physiology
  • Bruch Membrane / blood supply
  • Choroid / blood supply*
  • Complement Activation / physiology*
  • Complement System Proteins / genetics
  • Complement System Proteins / physiology*
  • Humans
  • Macular Degeneration / genetics
  • Macular Degeneration / immunology*
  • Macular Degeneration / physiopathology
  • Retinal Pigment Epithelium / blood supply


  • Complement System Proteins