Abstract

DO.02.05

AMD: A systemic disease?

Hendrik P. N. Scholl
Universitäs-Augenklinik Bonn

The heritability of age-related macular degeneration (AMD) has been estimated to be up to 71%. [1] In 2005, two significant genetic risk variant were identified: one variant (Y402H) in a gene on the long arm of chromosome 1 coding for complement factor H (CFH) and another (A69S) on the long arm of chromosome 10 coding for a gene named LOC387715). [2] Further genetic variants associated with disease risks were identified of which many belong to the innate immune system, the complement system: factor B (BF) and C3. Carriers of all risk or all protective variants in CFH, LOC387715, and BF, carry a 14-fold increased or 20-fold decreased risk, respectively, for AMD compared to baseline. [3]
There is now compelling evidence that the complement system is involved in the pathogenesis of AMD. It represents a complex system of plasma proteins. The direct consequences of the genetic variants in complement genes remain unknown. However, it was shown recently that there is systemic complement activation in AMD and that the genetic variants are associated with such systemic alteration of protein levels in the blood plasma. [4] AMD therefore appears to be a systemic disease and the macula represents the anatomic site where the disease manifests because of a specific vulnerability. However, systemic intervention for therapy or prophylaxis may have substantial risk because the complement system is a central element of the human immune system.
br>1. Seddon JM, Cote J, Page WF, Aggen SH, Neale MC (2005) Arch Ophthalmol 123:321-7.
2. Scholl HPN, Fleckenstein M, Issa PC, Keilhauer C, Holz FG, Weber BH (2007) Mol Vis 13:196-205.
3. Despriet DD, Klaver CC, van Duijn, Janssens AC (2007) Arch Ophthalmol. 125:1270-1.
4. Scholl HPN, Charbel Issa P, Walier M, Janzer S, Pollok-Kopp B, Börncke F, Fritsche LG, Chong NV, Fimmers R, Wienker T, Holz FG, Weber BH, Oppermann M. (2008) PLoS ONE 3(7):e2593.

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