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Editors Selection IGR 18-3

Basic Research: Aqueous humor protein composition and IOP

Comment by Sanjoy Bhattacharya on:

28124 Proteomic analysis of aqueous humor from patients with primary open angle glaucoma, Duan X; Xue P; Wang N et al., Molecular Vision, 2010; 16: 2839-2846

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Do aqueous humor (AH) protein composition changes play a role in IOP elevation and development of optic neuropathy in glaucoma? Duan et al. (95) asked the question, whether potential biomarkers for glaucoma can be identified by proteomic analyses of AH from patients with primary open-angle glaucoma (POAG) and non-glaucomatous patients undergoing cataract surgery. They analyzed AH from five individuals in each category (five POAG and five controls) utilizing an intermediate resolution and accuracy mass spectrometer. Prior to mass spectrometry they used two-dimensional (2D) gel electrophoresis for fractionation and identification of differential spots in the glaucomatous AH. Eight spots that showed significant increase in protein amounts were identified as prostaglandin H2 D isomerase (PGDS), caspase 14 precursor, transthyretin, cystain C, albumin precursor, and transferrin. The information pertaining to identified proteins might offer new insights to reveal the mechanistic aberrations involved towards developing POAG. A similar study (Izzotti et al., 2010) has been reported utilizing protein array and ten POAG and 14 control (seven each male and female) that found 31 proteins significantly altered in POAG patients. The altered proteins in POAG are not common between these two studies. Recent comparative and quantitative (iTRAQ®) analysis of the protein content of AH from cataract (control) patients by mass spectrometry (Bennett et al., 2011) and tear analysis (Ananthi et al., 2011) has shown tremendous variability among individuals. Tremendous gender variability was also recorded in these quantitative studies.

The differential proteomics of ocular tissue derived fluid or tissues will yield limited information that then need to be followed up longitudinally with model systems

While transthyretin has been proposed as one of the significantly altered proteins in POAG, however, tremendous variability has been found among control patients by a few mass spectrometric studies. Comparative proteomics of AH will provide a differential list, however, determination of mechanistic involvement will necessitate a long term longitudinal follow up in appropriate model systems. The accuracy of peptide mass determinations and false positive identification are issues in these studies. However, the identification and quantification of low abundance proteins/peptides are major issues for these studies. Towards a biomarker discovery, it has to be borne in mind that for a disease like Glaucoma, the useful biomarkers should be predictors of susceptibility. The differential proteomics of ocular tissue derived fluid or tissues will yield limited information that then need to be followed up longitudinally with model systems.

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