title: Functional analysis of misfolded transthyretin extracted from abnormal vitreous with high myopia related ocular pathologies.
abstract: BACKGROUND
  In the development of high myopia, some secondary ocular diseases such as macular detachment (MD) and macular hole (MH) may occur owing to the elongation of the eyeball. Higher concentrations of misfolded transthyretin (TTR) had been detected in abnormal vitreous humor, but the mechanisms are still unclear.
  
  
  METHODS
  TTRs of high myopia and healthy vitreous were purified with TTR polyclonal antibody-Sepharose. Gel exclusion chromatography, cleavage activity assay and a fluorescent probe were employed for the functional comparison of natural and abnormal TTRs.
  
  
  RESULTS
  Compared with natural transthyretin, MH TTR showed lower retinol-binding protein (RBP) binding ability; and MD TTR could not bind with RBP at all. Additionally, MH and MD TTR did not reveal cleavage activity against apolipoprotein AI (apoA-I). Furthermore, the kinetic parameters of the interactions between abnormal TTRs and a thyroxine-like fluorescent probe were quite different from those of natural TTR.
  
  
  CONCLUSIONS
  The results suggested that misfolded TTRs in MD and MH patients' vitreous completely or partially lost natural bio-functions; and this should be associated with abnormal high TTR levels.
authors.affiliation: Department of Ophthalmology, The Wuxi People's Hospital, 299 Qing yang Road, Wuxi 214023, People's Republic of China. shaojun1983@gmail.com
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.forename: Yu
authors.initials: Y
authors.lastname: Xin
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000378:metabolism; D016022:Case-Control Studies; D002850:Chromatography, Gel; D005136:Eye Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000378:metabolism* / Q000473:pathology; D011228:Prealbumin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D059748:Proteolysis; D057165:Proteostasis Deficiencies / Q000378:metabolism* / Q000473:pathology; D012167:Retinal Perforations / Q000378:metabolism* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000378:metabolism; D013974:Thyroxine / Q000737:chemistry; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology; D020255:Vitreous Detachment / Q000378:metabolism* / Q000473:pathology
chemical_list: D016632:Apolipoprotein A-I; D005136:Eye Proteins; D005456:Fluorescent Dyes; D011228:Prealbumin; D012177:Retinol-Binding Proteins; D013974:Thyroxine