Anti-fumarase antibody promotes the dropout of photoreceptor inner and outer segments in diabetic macular oedema
| Autor: | Yoko Dodo, Patrice Fort, Akitaka Tsujikawa, Tomoaki Murakami, Masahiro Fujimoto, Akihito Uji, Yang Shan, Nagahisa Yoshimura, Shinji Ito, Shin Yoshitake, Satoshi Morooka, Tatsuya Yoshitake, Kiyoshi Suzuma |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine genetic structures Endocrinology Diabetes and Metabolism Cell 030209 endocrinology & metabolism Macular Edema Article Fumarate Hydratase 03 medical and health sciences 0302 clinical medicine Internal Medicine Humans Medicine Pathological Neuroinflammation Autoantibodies chemistry.chemical_classification Diabetic Retinopathy biology business.industry Autoantibody Complement system 030104 developmental biology Enzyme medicine.anatomical_structure chemistry Immunoglobulin G Fumarase Immunology biology.protein Female Antibody business Photoreceptor Cells Vertebrate |
| Zdroj: | Diabetologia. 62:504-516 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-018-4773-1 |
| Popis: | AIMS/HYPOTHESIS: In diabetic macular oedema (DMO), blood components passing through the disrupted blood-retinal barrier cause neuroinflammation, but the mechanism by which autoantibodies induce neuroglial dysfunction is unknown. The aim of this study was to identify a novel autoantibody and to evaluate its pathological effects on clinically relevant photoreceptor injuries. METHODS: Biochemical purification and subsequent peptide fingerprinting were applied to identify autoantigens. The titres of autoantibodies in DMO sera were quantified and their associations with clinical variables were evaluated. Two animal models (i.e. passive transfer of autoantibodies and active immunisation) were characterised with respect to autoimmune mechanisms underlying photoreceptor injuries. RESULTS: After screening serum IgG from individuals with DMO, fumarase, a Krebs cycle enzyme expressed in inner segments, was identified as an autoantigen. Serum levels of anti-fumarase IgG in participants with DMO were higher than those in diabetic participants without DMO (p |
| Databáze: | OpenAIRE |
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