Survey of Ophthalmology
Volume 51, Issue 2 , Pages 137-152, March 2006

The Role of Inflammation in the Pathogenesis of Age-related Macular Degeneration

  • Larry A. Donoso, MD, PhD

      Affiliations

    • The Henry and Corinne Bower Laboratory, the Eye Research Institute, Wills Eye Hospital, Philadelphia, Pennsylvania
    • International Retinal Research Foundation, Birmingham, Alabama
    • Corresponding Author InformationReprint address: Larry A. Donoso, MD, PhD, Bower Research Laboratory, P.O. Box 53429, Philadelphia, PA 19105.
  • ,
  • David Kim

      Affiliations

    • The Henry and Corinne Bower Laboratory, the Eye Research Institute, Wills Eye Hospital, Philadelphia, Pennsylvania
  • ,
  • Arcilee Frost

      Affiliations

    • The Henry and Corinne Bower Laboratory, the Eye Research Institute, Wills Eye Hospital, Philadelphia, Pennsylvania
  • ,
  • Alston Callahan, MD

      Affiliations

    • International Retinal Research Foundation, Birmingham, Alabama
  • ,
  • Gregory Hageman, PhD

      Affiliations

    • Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa, USA

EDWARD COTLIER AND ROBERT WEINREB, EDITORS

Abstract 

Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is a complex disease to study because of the potential role of demographic, environmental, and other systemic risk factors, such as age, sex, race, light exposure, diet, smoking, and underlying cardiovascular disease which may contribute to the pathogenesis of this disease. Recently, single nucleotide polymorphisms, DNA sequence variations found within the complement Factor H gene, have been found to be strongly associated with the development of AMD in Caucasians. One single nucleotide polymorphism, Tyr402His, was associated with approximately 50% of AMD cases. We review recent developments in the molecular biology of AMD, including single nucleotide polymorphisms within the Factor H gene, which may predispose individuals to the susceptibility of AMD as well as single nucleotide polymorphisms that may confer a protective effect. Taken together these findings help to provide new insights into the central issues surrounding the pathogenesis of AMD.

Key words: age-related macular degeneration, atherosclerosis, complement, drusen, Factor H gene, genetics, glomerulonephritis, inflammation, single nucleotide polymorphism

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 The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article. This manuscript is dedicated to Alston Callahan, MD, (1911–2005) and to Charles D. Kelman, MD, (1930–2004) two of the co-founders of the International Retinal Research Foundation. Dr. Callahan contributed directly to this manuscript and his help is greatly appreciated. The manuscript was supported, in part, by the Henry and Corinne Bower Laboratory, the Eye Research Institute, and the Elizabeth C. King Trust. The support of L. Stanley Mauger is greatly appreciated. Sandra Blackwood and Thomas Perski provided helpful discussions.

PII: S0039-6257(05)00206-7

doi:10.1016/j.survophthal.2005.12.001

Survey of Ophthalmology
Volume 51, Issue 2 , Pages 137-152, March 2006