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Abstract
Abstarct
Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were found linked with pathophysiology of Alzheimer’s disease (AD). Pathway analyses of differentially regulated proteins indicate defects in mitochondrial oxidative phosphorylation machinery. The classical complement pathway associated proteins were activated in the glaucoma samples suggesting an innate inflammatory response. The majority of common differentially regulated proteins in both tissues were members of functional protein networks associated brain changes in AD and other chronic degenerative conditions. Identification of previously reported and novel pathways in glaucoma that overlap with other CNS neurodegenerative disorders promises to provide renewed understanding of the aetiology and pathogenesis of age related neurodegenerative diseases.
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Details
1 Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia
2 School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia
3 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
4 Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
5 Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia
6 Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
7 Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia
8 Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; Save Sight Institute, Sydney University, Sydney, NSW, Australia
9 Department of Molecular Systems Biology, Cell Science Research Center, Royan, Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
10 Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW, Australia; Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW, Australia
11 School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia