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Updated: Apr 24, 2026
Enrichment of Bruch's Membrane from Human Donor Eyes
Published on: November 15, 2015
The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal
Robert F Mullins1, Desi P Schoo1, Elliott H Sohn1
1Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, Iowa.
Insights
The membrane attack complex (MAC) increases with aging and age-related macular degeneration (AMD). Complement factor H (CFH) risk genotypes are linked to thinner choroids, suggesting early AMD involves endothelial cell loss.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- Abnormal complement system regulation and CFH gene polymorphisms are implicated in AMD pathogenesis.
- The precise mechanisms by which CFH polymorphisms contribute to AMD risk remain unclear.
Purpose of the Study:
- To investigate the role of the membrane attack complex (MAC) in AMD pathogenesis.
- To correlate MAC abundance with aging, AMD progression, and CFH genotypes.
- To explore potential therapeutic targets for early AMD.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) on choroidal tissues from young, aged, and AMD patients.
- Immunofluorescence studies on donor eyes (n=117) across different stages of aging and AMD.
- Morphometric analysis of choroidal thickness in relation to CFH genotypes.
Main Results:
- MAC levels significantly increase with both aging and AMD.
- MAC is localized to Bruch's membrane and choriocapillaris, appearing even in early childhood.
- High-risk CFH genotypes are associated with thinner choroids, suggesting early endothelial cell damage.
Conclusions:
- Increased complement activation, evidenced by MAC, is a key feature of AMD and is influenced by CFH risk variants.
- Early AMD may involve complement-mediated loss of choriocapillaris endothelial cells.
- Developing treatments to protect the choriocapillaris in early AMD is crucial.
Abstract:
Age-related macular degeneration (AMD) is a common disease that can result in severe visual impairment. Abnormal regulation of the complement system has been implicated in its pathogenesis, and CFH polymorphisms contribute substantially to risk. How these polymorphisms exert their effects is poorly understood. We performed enzyme-linked immunosorbent assay (ELISA) analysis on young, aged, and AMD choroids to determine the abundance of the membrane attack complex (MAC) and performed immunofluorescence studies on eyes from 117 donors to evaluate the MAC in aging, early AMD, and advanced AMD. Morphometric studies were performed on eyes with high- or low-risk CFH genotypes. ELISA confirmed that MAC increases significantly with aging and with AMD. MAC was localized to Bruch's membrane and the choriocapillaris and was detectable at low levels as early as 5 years of age. Hard drusen were labeled with anti-MAC antibody, but large or confluent drusen and basal deposits were generally unlabeled. Labeling of retinal pigment epithelium was observed in some cases of advanced AMD, but not in early disease. Eyes homozygous for the high-risk CFH genotype had thinner choroids than low-risk homozygotes (P < 0.05). These findings suggest that increased complement activation in AMD and in high-risk genotypes can lead to loss of endothelial cells in early AMD. Treatments to protect the choriocapillaris in early AMD are needed.
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