title: Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?
abstract: Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (β2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of β2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate β2GPI in the retina and choroid of patients with AMD. Free thiol β2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of β2GPI and free thiol bovine serum albumin were not protective. Free thiol β2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol β2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Miao
authors.initials: M
authors.lastname: Qi
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdelatti
authors.affiliation: 3 Save Sight Institute, University of Sydney and Sydney Eye Hospital , Sydney, New South Wales, Australia .
authors.forename: Matthew
authors.initials: M
authors.lastname: Krilis
authors.affiliation: 3 Save Sight Institute, University of Sydney and Sydney Eye Hospital , Sydney, New South Wales, Australia .|4 School of Optometry and Vision Science, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Michele C
authors.initials: MC
authors.lastname: Madigan
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|5 Department of Cardiology, St. George Hospital , Sydney, New South Wales, Australia .
authors.forename: James
authors.initials: J
authors.lastname: Weaver
authors.affiliation: 6 Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne , Melbourne, Victoria, Australia .
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.affiliation: 3 Save Sight Institute, University of Sydney and Sydney Eye Hospital , Sydney, New South Wales, Australia .
authors.forename: Peter
authors.initials: P
authors.lastname: McCluskey
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Saijun
authors.initials: S
authors.lastname: Zhou
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Steven A
authors.initials: SA
authors.lastname: Krilis
authors.affiliation: 1 Department of Infectious Diseases, Immunology and Sexual Health, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .|2 Department of Medicine, St. George Hospital, University of New South Wales , Sydney, New South Wales, Australia .
authors.forename: Bill
authors.initials: B
authors.lastname: Giannakopoulos
mesh_terms: D000818:Animals; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008268:Macular Degeneration / Q000378:metabolism* / Q000503:physiopathology*; D012160:Retina / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D053482:beta 2-Glycoprotein I / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D004220:Disulfides; D053482:beta 2-Glycoprotein I; D012710:Serum Albumin, Bovine; D006861:Hydrogen Peroxide