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.

Abstract

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.

• Authors: Anandalakshmi Venkatraman, Guillaume Hochart, David Bonnel, Jonathan Stauber, Shigeto Shimmura, Lakshminaryanan Rajamani, Konstantin Pervushin, Jodhbir S Mehta
• Journal: Proteomics. Clinical applications (Proteomics Clin Appl) Vol. 13 Issue 1 Pg. e1800053 (01 2019) ISSN: 1862-8354 [Electronic] Germany
• PMID: 30387319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Transforming Growth Factor beta

Topics

• Cornea (diagnostic imaging, metabolism)
• Corneal Dystrophies, Hereditary (diagnostic imaging, genetics, metabolism)
• Humans
• Molecular Imaging
• Mutation
• Proteomics
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Transforming Growth Factor beta (genetics, metabolism)