What is the pathophysiology of age-related macular degeneration (AMD)?

Updated: Dec 12, 2018
  • Author: Lucia Sobrin, MD, MPH; Chief Editor: Karl S Roth, MD  more...
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Answer

Answer

Even before the identification of the genetic associations described above, the inflammatory cascade had been thought to be an important component in the pathophysiology of AMD, [28]  and a study showed that a marker of systemic inflammation, C-reactive protein, was related to AMD. [3]  The existence of multiple, complement-related AMD risk alleles has lent further support to this theory and has shed light on the role of uncontrolled alternative complement pathway activation in this disease.

CFH inhibits the alternative complement pathway by blocking formation and accelerating the decay of alternative pathway C3 convertases; it also serves as a cofactor for the factor-1 mediated cleavage and inactivation of C3b. [29] The Y402H variant is within the CFH binding site for heparin and C-reactive protein. Binding to these sites increases the affinity of CFH for C3b, which, in turn, increases the ability of CFH to inhibit complement's effects.


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