title: Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation.
abstract: AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behçet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-κB p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-κB.
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan;
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Daiju
authors.initials: D
authors.lastname: Iwata
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan; nobukita@med.hokudai.ac.jp.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.affiliation: Division of Advanced Glycation End-products Research, Department of Advanced Medicine, Kanazawa Medical University, Kanazawa, Japan;
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan; and.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan; and.
authors.forename: Noriko
authors.initials: N
authors.lastname: Endo
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara, Japan; and.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Ryo
authors.initials: R
authors.lastname: Ando
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Junichi
authors.initials: J
authors.lastname: Fukuhara
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kinoshita
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Anton
authors.initials: A
authors.lastname: Lennikov
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Mizuki
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Mizuuchi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Kenichi
authors.initials: K
authors.lastname: Namba
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001528:Behcet Syndrome / Q000097:blood / Q000150:complications; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005136:Eye Proteins / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D021381:Protein Transport / Q000187:drug effects; D011733:Pyridoxamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012160:Retina / Q000378:metabolism; D012173:Retinitis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000633:toxicity; D012507:Sarcoidosis / Q000097:blood / Q000150:complications; D014605:Uveitis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014607:Uveomeningoencephalitic Syndrome / Q000097:blood / Q000150:complications; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D017127:Glycation End Products, Advanced; D015796:HLA-B27 Antigen; D010446:Peptide Fragments; D011733:Pyridoxamine; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial
keywords: EAU; diabetic iritis; glycer-AGE; pyridoxamine; uveitis