The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning

Robert F Mullins; Desi P Schoo; Elliott H Sohn; Miles J Flamme-Wiese; Grefachew Workamelahu; Rebecca M Johnston; Kai Wang; Budd A Tucker; Edwin M Stone

doi:10.1016/j.ajpath.2014.07.017

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The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning

Journal article

Open access

Peer reviewed

The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning

Robert F Mullins, Desi P Schoo, Elliott H Sohn, Miles J Flamme-Wiese, Grefachew Workamelahu, Rebecca M Johnston, Kai Wang, Budd A Tucker and Edwin M Stone

The American journal of pathology, Vol.184(11), pp.3142-3153

11/2014

DOI: 10.1016/j.ajpath.2014.07.017

PMCID: PMC4215023

PMID: 25204844

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https://doi.org/10.1016/j.ajpath.2014.07.017View

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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.

Retinal Pigment Epithelium - metabolism

Complement Membrane Attack Complex - metabolism

Humans

Middle Aged

Child, Preschool

Infant

Male

Complement Membrane Attack Complex - genetics

Young Adult

Retinal Pigment Epithelium - pathology

Aging - genetics

Aged, 80 and over

Adult

Female

Choroid - pathology

Infant, Newborn

Choroid - metabolism

Aging - pathology

Macular Degeneration - metabolism

Complement Factor H - metabolism

Macular Degeneration - genetics

Aged

Complement Factor H - genetics

Aging - metabolism

Macular Degeneration - pathology

Details

Title: Subtitle: The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning
Creators: Robert F Mullins - Department 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. Electronic address: robert-mullins@uiowa.edu
Desi P Schoo - Department 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
Elliott H Sohn - Department 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
Miles J Flamme-Wiese - Department 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
Grefachew Workamelahu - Department 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
Rebecca M Johnston - Department 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
Kai Wang - Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, Iowa; Department of Biostatistics, The University of Iowa, Iowa City, Iowa
Budd A Tucker - Department 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
Edwin M Stone - Department 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
Resource Type: Journal article
Publication Details: The American journal of pathology, Vol.184(11), pp.3142-3153
DOI: 10.1016/j.ajpath.2014.07.017
PMID: 25204844
PMCID: PMC4215023
NLM abbreviation: Am J Pathol
ISSN: 1525-2191
eISSN: 1525-2191
Publisher: United States
Grant note: R01EY016822 / NEI NIH HHS R01EY017451 / NEI NIH HHS R01 EY016822 / NEI NIH HHS DP2 OD007483 / NIH HHS Howard Hughes Medical Institute DP2-OD007483-01 / NIH HHS R01 EY017451 / NEI NIH HHS
Language: English
Date published: 11/2014
Academic Unit: Iowa Neuroscience Institute; Biostatistics; Ophthalmology and Visual Sciences
Record Identifier: 9983979989702771

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