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Complement factor H variant Y402H and basal laminar deposits in exudative age-related macular degeneration
Albrecht Lommatzsch1, Pia Hermans, Bernhard Weber
1Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 Münster, Germany.
Insights
Basal laminar deposits in age-related macular degeneration contain complement factor H (CFH) and vitronectin. The CFH Y402H polymorphism, linked to AMD, may increase vitronectin secretion due to complement dysregulation.
Area of Science:
- Ophthalmology
- Immunogenetics
- Molecular Biology
Background:
- Age-related macular degeneration (AMD) is associated with Complement Factor H (CFH) Y402H polymorphism.
- Basal laminar deposits (BLD) in AMD are implicated in choroidal neovascularization (CNV).
Purpose of the Study:
- To correlate CFH staining within BLD with the CFH Y402H genotype.
Main Methods:
- CNV membranes from 21 patients were analyzed histologically for BLD.
- Immunohistochemistry was used to detect CFH, complement proteins (C3, C5b-9), and vitronectin in BLD.
- CFH Y402H genotyping was performed via direct sequencing.
Main Results:
- BLD were present in all excised CNV membranes.
- CFH, C3, C5b-9, and vitronectin were detected within BLD.
- Patient genotypes for CFH Y402H polymorphism included noncarriers, heterozygotes, and homozygotes.
Conclusions:
- BLD comprise complement factors (CFH, C3, C5b-9) and vitronectin.
- Homozygous carriers of the CFH Y402H polymorphism may exhibit increased vitronectin secretion.
- This may be linked to complement cascade dysregulation in AMD pathogenesis.
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.
Patients And 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.
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