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Aberrant glycosylation in the human trabecular meshwork
Article first published online: 7 MAR 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Focus on Proteomics and the Eye
Volume 8, Issue 3-4, pages 130–142, April 2014
How to Cite
Sienkiewicz, A. E., Rosenberg, B. N., Edwards, G., Carreon, T. A. and Bhattacharya, S. K. (2014), Aberrant glycosylation in the human trabecular meshwork. Prot. Clin. Appl., 8: 130–142. doi: 10.1002/prca.201300031
- Issue published online: 13 APR 2014
- Article first published online: 7 MAR 2014
- Accepted manuscript online: 23 JAN 2014 10:02PM EST
- Manuscript Accepted: 14 OCT 2013
- Manuscript Revised: 19 SEP 2013
- Manuscript Received: 24 APR 2013
- NIH. Grant Numbers: EY016112, EY016112S1, P30-EY14801
- Computational Ocular Genomics Training. Grant Number: T32EY023194-01
- Carbohydrate electrophoresis;
- Trabecular meshwork
To determine the difference in protein glycosylation and glycosylation enzyme levels between glaucomatous and control trabecular meshwork (TM).
Glaucomatous and normal donor (n = 12 each) TM tissues, lectin fluorescence, fluorophore-assisted carbohydrate analyses, and quantitative MS were used to determine the glycosylation levels. Primary TM cells and glycosylation inhibitors were used to determine their effect on cell shape and motility.
In contrast to elevated levels of glycoproteins determined by lectin fluorescence, simultaneous hyper- and hypo-glycosylation in glaucomatous TM was revealed by fluorophore-assisted carbohydrate analyses. Analyses of enzymes showed elevation of beta-glycosidase 1 and decrease in galactosyltransferase family 6 domain containing protein 1 in the glaucomatous TM. Quantitative MS identified select protein level changes between glaucomatous and normal TM. Primary TM cells were treated with inhibitors to elicit hypo-glycosylation, which affected cell shape, motility, and fluorescent tracer transport across a layer of TM cells.
Conclusions and clinical relevance
Global protein glycosylation is aberrant in glaucomatous TM compared to controls. The results presented here suggest that the alteration in global TM protein glycosylation encompassing cellular and extracellular matrix proteins contributes to glaucoma pathology likely mediated through changes in properties of TM cells.