Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes

Abstract

AbstarctGlaucoma 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.

Binding of a glaucoma-associated myocilin variant to the αB-crystallin chaperone impedes protein clearance in trabecular meshwork cells

“…There is established precedence in the literature confirming an association between CRYAB levels and disease with CRYAB showing modified expression in glaucoma models of high IOP (56,57). Additionally, analysis of the human vitreous humor proteome found that expression of numerous crystallin family proteins are significantly down-regulated in glaucomatous eyes (58).…”

TMT Labeling for the Masses: A Robust and Cost-efficient, In-solution Labeling Approach

“…One substantial shortcoming of quantification by isobaric labeling is the high cost of reagents. We and others have previously reported protocols in which the amount of TMT reagent recommended by the vendor was reduced (6 -10) and successfully applied such economically optimized labeling workflows to address a variety of biological questions (3,(11)(12)(13). However, details on the quantities and concentrations of reactants vary widely in the published literature and, to the best of our knowledge, no systematic evaluation of the influence of reducing TMT-to-peptide ratios on the overall labeling performance has been reported to date.…”

Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?

“…Deposits of amyloid β protein, synuclein, and pTau have been detected in the retinas of patients suffering from glaucoma. In addition, a recent proteomics study on the vitreous humor of glaucomatous patients found that 100 differentially regulated proteins are common to the pathophysiology of Alzheimer's disease [100]. Like neurodegenerative diseases, glaucoma produces neuroinflammatory reactions, particularly with regard to the activation of glial and microglial cells [101].…”