title: Marked biochemical difference in amyloid proportion between intra- and extraocular tissues in a liver-transplanted patient with hereditary ATTR amyloidosis.
abstract: In order to elucidate the pathomechanism of ocular amyloid formation in a liver-transplanted patient with hereditary ATTR amyloidosis, we investigated detailed biochemical features of ocular amyloid. The patient was a 49-year-old woman with V30M transthyretin (TTR) variant (p.TTRV50M), who underwent ophthalmectomy due to corneal rupture 10 years after liver transplantation (LT). The amyloid was selectively isolated from several portions in intra- and extraocular tissues using a laser microdissection (LMD) system and analyzed by liquid chromatography-tandem mass spectrometry to determine the composition percentage of wild-type and variant TTR in the isolated amyloid. Biochemical analysis revealed that the amyloid consisted mainly of variant TTR in intraocular tissues with a percentage > 80%. On the contrary in the extraocular muscles, wild-type TTR was the main component of the amyloid with a percentage of ∼70%. Our data indicate that intraocular amyloid formation strongly depends on locally synthesized variant TTR and the contribution of wild-type TTR to amyloid formation is quite limited.
authors.affiliation: a Department of Medicine (Neurology and Rheumatology) , Shinshu University School of Medicine , Matsumoto , Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Yoshinaga
authors.affiliation: a Department of Medicine (Neurology and Rheumatology) , Shinshu University School of Medicine , Matsumoto , Japan.|b Department of Biological Sciences for Intractable Neurological Diseases , Institute for Biomedical Sciences, Shinshu University , Matsumoto , Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Yazaki
authors.affiliation: c Department of Dementia and Higher Brain Function , Tokyo Metropolitan Institute of Medical Science , Tokyo , Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Kametani
authors.affiliation: a Department of Medicine (Neurology and Rheumatology) , Shinshu University School of Medicine , Matsumoto , Japan.|b Department of Biological Sciences for Intractable Neurological Diseases , Institute for Biomedical Sciences, Shinshu University , Matsumoto , Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sekijima
authors.affiliation: d Department of Ophthalmology , Shinshu University School of Medicine , Matsumoto , Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iesato
authors.affiliation: d Department of Ophthalmology , Shinshu University School of Medicine , Matsumoto , Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Miyahara
authors.affiliation: a Department of Medicine (Neurology and Rheumatology) , Shinshu University School of Medicine , Matsumoto , Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya-Suzuki
authors.affiliation: e Department of Laboratory Medicine , Shinshu University School of Medicine , Matsumoto , Japan , and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.affiliation: b Department of Biological Sciences for Intractable Neurological Diseases , Institute for Biomedical Sciences, Shinshu University , Matsumoto , Japan.|f Department of Aging Biology , Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine , Mastumoto , Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: a Department of Medicine (Neurology and Rheumatology) , Shinshu University School of Medicine , Matsumoto , Japan.
authors.forename: Shu-Ichi
authors.initials: SI
authors.lastname: Ikeda
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000628:therapy*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D016031:Liver Transplantation; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000682:Amyloid; D011228:Prealbumin
keywords: Laser microdissection; hereditary ATTR amyloidosis; liver transplantation; ocular amyloidosis; transthyretin