title: The membrane attack complex in aging human choriocapillaris: relationship to macular degeneration and choroidal thinning.
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.
authors.affiliation: 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.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.affiliation: 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.
authors.forename: Desi P
authors.initials: DP
authors.lastname: Schoo
authors.affiliation: 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.
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sohn
authors.affiliation: 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.
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Flamme-Wiese
authors.affiliation: 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.
authors.forename: Grefachew
authors.initials: G
authors.lastname: Workamelahu
authors.affiliation: 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.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Johnston
authors.affiliation: Stephen A. Wynn Institute for Vision Research, The University of Iowa, Iowa City, Iowa; Department of Biostatistics, The University of Iowa, Iowa City, Iowa.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.affiliation: 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.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002675:Child, Preschool; D002829:Choroid / Q000378:metabolism / Q000473:pathology*; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015938:Complement Membrane Attack Complex; D017242:Complement Factor H