Complement factor H variant Y402H and basal laminar deposits in exudative age-related macular degeneration.
BACKGROUND
Complement factor H (CFH) polymorphism Y402H has been shown to be significantly associated with age-related macular degeneration (AMD). Furthermore, histopathological studies in AMD have implicated basal laminar deposits (BLD) in the development of choroidal neovascularization (CNV) membranes. The purpose of this study was to correlate CFH staining in BLD with the CFH genotype at the tyrosine 402 histidine (Y402H) polymorphism.


METHODS
During macular translocation, 21 angiographically confirmed CNV membranes were extracted in 21 patients. The specimens were analysed histologically for BLD. The presence of CFH, complement proteins, and vitronectin was determined by immunohistochemistry. Finally, the CFH Y402H genotype was established by direct sequencing analysis.


RESULTS
Histological examination demonstrated BLD in all of the excised CNV membranes. By immunostaining CFH was detected in the peripheral aspect at the inner and outer surface of BLD, which colocalized with other proteins of the complement cascade (C3, C5b-9). Similarly, vitronectin was detected in all of the BLD investigated. Four patients were noncarriers of CFH Y402H polymorphism, nine patients were heterozygous and eight patients homozygous for the CFH Y402H polymorphism.


CONCLUSIONS
BLD are composed of different complement factors (factor H, C3, C5b-9) and extracellular matrix proteins such as vitronectin. The prevalence of homozygous carriers in regard to CFH Y402H polymorphism, which is suspicious for AMD, might be associated with increased secretion of vitronectin in response to dysregulation of the complement cascade.
Lommatzsch
Albrecht
A
Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 Münster, Germany.
Hermans
Pia
P
Weber
Bernhard
B
Pauleikhoff
Daniel
D
D000368:Aged; D000369:Aged, 80 and over; D001485:Basement Membrane / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D005122:Exudates and Transudates; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019096:Vitronectin / Q000378:metabolism
C493495:CFH protein, human; D019096:Vitronectin; D017242:Complement Factor H
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