Proteomics

Dataset Information

14

Biomechanical rigidity and quantitative proteomics analyses of segmental regions of the ocular trabecular meshwork at physiologic and elevated pressures


ABSTRACT: The extracellular matrix (ECM) of the ocular trabecular meshwork (TM) builds resistance to aqueous humor outflow, thereby regulating intraocular pressure (IOP). Glaucoma, a leading cause of blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus indicates glaucomatous TM is more rigid than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions in response to elevated pressure, are unknown. In this study, we measured the elastic modulus by atomic force microscopy (AFM) and measured protein expression differences in perfused human TM tissues by proteomics analyses. The elastic modulus of LF regions was 2.3-fold stiffer than HF regions at physiological (1x) pressure, and 7.4-fold or 3.5-fold stiffer than HF regions at elevated (2x) pressure after 24 or 72 hours, respectively. Quantitative proteomics using isobaric tandem mass tags (TMT), multi-notch isolation, high resolution, and extended multiplexing were used to compare protein expression levels between normal, LF, and HF regions at the two pressures. A total of 3730 proteins (2 peptides per protein) were identified from the ECM samples, and 2637 proteins were quantified. Statistically significant ECM proteins over expressed in LF compared with HF regions at 2x, and in HF regions at 1x compared with 2x pressure were determined. A sub-set of ECM proteins, including decorin, TGFβ-induced protein, keratocan, lumican, dermatopontin and thrombospondin 4, were common differential candidates in both comparisons. These data suggest a correlation between the biomechanical properties of TM regions and differential levels of specific ECM proteins in response to elevated pressure.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo sapiens  

TISSUE(S): Eye

DISEASE(S): Glaucoma

SUBMITTER: Phillip Wilmarth  

PROVIDER: PXD006424 | Pride | 2018-01-22

REPOSITORIES: Pride

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Publications

Biomechanical Rigidity and Quantitative Proteomics Analysis of Segmental Regions of the Trabecular Meshwork at Physiologic and Elevated Pressures.

Vranka Janice A JA   Staverosky Julia A JA   Reddy Ashok P AP   Wilmarth Phillip A PA   David Larry L LL   Acott Ted S TS   Russell Paul P   Raghunathan Vijay Krishna VK  

Investigative ophthalmology & visual science 20180101 1


The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading cause of irreversible blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus of glaucomatous TM is larger than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions and their response to elevated pressure, are unknown.We perfused human anterior segment  ...[more]

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