Activation of the alternative complement pathway in vitreous is controlled by genetics in age-related macular degeneration.
Invest Ophthalmol Vis Sci
; 53(10): 6628-37, 2012 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-22930722
ABSTRACT
PURPOSE:
To determine if the progression of age-related macular degeneration (AMD) is associated with complement activation in the eye.METHODS:
Immunohistochemistry and ELISAs were used to determine the distribution, concentration, and activation of the alternative pathway complement proteases factor B (FB) and factor D (FD) and the central complement protein C3 in genotyped human postmortem donor eyes graded as having no or minimal drusen (category 1; controls), large drusen (category 3), and large drusen with advanced AMD (category 4).RESULTS:
C3, FB, and FD were present in vitreous and Bruch's membrane choroid (BM/C) interface of the macula of eyes in all tested AMD severity categories (n = 100). C3, FB, and FD were predominantly located to the choroidal vasculature and Bruch's membrane and, together with the serum proteins transferrin and albumin, elevated in BM/C extracts of category 4 eyes (n = 23) compared with category 1 eyes (n = 24). A significant increase in FB activation was found only in vitreous of category 4 eyes (n = 23) compared with category 1 eyes (n = 25). Genetic variants of complement factor H (CFH), C3, C2, and FB associated with increased risk of AMD were correlated with alternative pathway complement activation in vitreous, but not with complement proteins in BM/C protein extracts.CONCLUSIONS:
Increased activation of the alternative complement pathway in vitreous was controlled by disease stage and genetic variation in the complement pathway, supporting a role for complement activation in AMD disease pathogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Corpo Vítreo
/
Complemento C3
/
Fator B do Complemento
/
Fator D do Complemento
/
Via Alternativa do Complemento
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Degeneração Macular
Limite:
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article