TY - JOUR
T1 - Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging of Key Proteins in Corneal Samples from Lattice Dystrophy Patients with TGFBI-H626R and TGFBI-R124C Mutations
AU - Venkatraman, Anandalakshmi
AU - Hochart, Guillaume
AU - Bonnel, David
AU - Stauber, Jonathan
AU - Shimmura, Shigeto
AU - Rajamani, Lakshminaryanan
AU - Pervushin, Konstantin
AU - Mehta, Jodhbir S.
N1 - Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/1
Y1 - 2019/1
N2 - Scope: The purpose of this study is to identify and visualize the spatial distribution of proteins present in amyloid corneal deposits of TGFBI-CD patients using Mass Spectrometry Imaging (MSI) and compare it with healthy control cornea. Corneal Dystrophies (CD) constitute a group of genetically inherited protein aggregation disorders that affects different layers of the cornea. With accumulated protein deposition, the cornea becomes opaque with decreased visual acuity. CD affecting the stroma and Bowman's membrane, is associated with mutations in transforming growth factor β-induced (TGFBI) gene. Methods: MALDI-Mass Spectrometry Imaging (MSI) is performed on 2 patient corneas and is compared with 1 healthy control cornea using a 7T-MALDI-FTICR. Molecular images obtained are overlaid with congo-red stained sections to visualize the proteins associated with the corneal amyloid aggregates. Results: MALDI-MSI provides a relative abundance and two dimensional spatial protein signature of key proteins (TGFBIp, Apolipoprotein A-I, Apolipoprotein A-IV, Apolipoprotein E, Kaliocin-1, Pyruvate Kinase and Ras related protein Rab-10) in the patient deposits compared to the control. This is the first report of the anatomical localization of key proteins on corneal tissue section from CD patients. This may provide insight in understanding the mechanism of amyloid fibril formation in TGFBI-corneal dystrophy.
AB - Scope: The purpose of this study is to identify and visualize the spatial distribution of proteins present in amyloid corneal deposits of TGFBI-CD patients using Mass Spectrometry Imaging (MSI) and compare it with healthy control cornea. Corneal Dystrophies (CD) constitute a group of genetically inherited protein aggregation disorders that affects different layers of the cornea. With accumulated protein deposition, the cornea becomes opaque with decreased visual acuity. CD affecting the stroma and Bowman's membrane, is associated with mutations in transforming growth factor β-induced (TGFBI) gene. Methods: MALDI-Mass Spectrometry Imaging (MSI) is performed on 2 patient corneas and is compared with 1 healthy control cornea using a 7T-MALDI-FTICR. Molecular images obtained are overlaid with congo-red stained sections to visualize the proteins associated with the corneal amyloid aggregates. Results: MALDI-MSI provides a relative abundance and two dimensional spatial protein signature of key proteins (TGFBIp, Apolipoprotein A-I, Apolipoprotein A-IV, Apolipoprotein E, Kaliocin-1, Pyruvate Kinase and Ras related protein Rab-10) in the patient deposits compared to the control. This is the first report of the anatomical localization of key proteins on corneal tissue section from CD patients. This may provide insight in understanding the mechanism of amyloid fibril formation in TGFBI-corneal dystrophy.
UR - http://www.scopus.com/inward/record.url?scp=85056719525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056719525&partnerID=8YFLogxK
U2 - 10.1002/prca.201800053
DO - 10.1002/prca.201800053
M3 - Article
C2 - 30387319
AN - SCOPUS:85056719525
SN - 1862-8346
VL - 13
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 1
M1 - 1800053
ER -