title: Localization of complement 1 inhibitor (C1INH/SERPING1) in human eyes with age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is a common degenerative disease resulting in injury to the retina, retinal pigment epithelium and choriocapillaris. Recent data from histopathology, animal models and genetic studies have implicated altered regulation of the complement system as a major factor in the incidence and progression of this disease. A variant in the gene SERPING1, which encodes C1INH, an inhibitor of the classical and lectin pathways of complement activation, was recently shown to be associated with AMD. In this study we sought to determine the localization of C1INH in human donor eyes. Immunofluorescence studies using a monoclonal antibody directed against C1INH revealed localization to photoreceptor cells, inner nuclear layer neurons, choriocapillaris, and choroidal extracellular matrix. Drusen did not exhibit labeling. Genotype at rs2511989 did not appear to affect C1INH abundance or localization, nor was it associated with significant molecular weight differences when evaluated by Western blot. In a small number of eyes (n = 7 AMD and n = 7 control) AMD affection status was correlated with increased abundance of choroidal C1INH. These results indicate that C1INH protein is present in the retina and choroid, where it may regulate complement activation.
authors.affiliation: Carver Family Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, The University of Iowa, 4135E MERF, 375 Newton Rd, Iowa City, IA 52242, USA. robert-mullins@uiowa.edu
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Faidley
authors.forename: Heather T
authors.initials: HT
authors.lastname: Daggett
authors.forename: Catherine
authors.initials: C
authors.lastname: Jomary
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D015153:Blotting, Western; D002196:Capillaries / Q000737:chemistry; D002829:Choroid / Q000098:blood supply / Q000737:chemistry*; D003174:Complement C1 Inactivator Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D050718:Complement C1 Inhibitor Protein; D005109:Extracellular Matrix / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry; D055351:Retinal Neurons / Q000737:chemistry*
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human