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A. C. Len, G. Hageman, M. C. Gillies; Taking a Quantitative Mass Spectrometry Based Approach to Identifying Putative Disease Biomarkers of Macular Telangiectasia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3994.
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Macular telangiectasia (MT) is a sight threatening eye condition affecting the retinal vascular system by a yet unknown mechanism and currently there is no recognized therapy. However, the identification of disease biomarkers may lead to development of treatments to prevent and even reverse loss of vision from MT. This can be achieved by analysing the vitreous, which may act as a buffer exchange medium to biomolecules such as proteins from the retina. This role may not change during disease; however, a differential protein profile may be expressed. Hence the altered protein profile of the vitreous may be a signature of retinal disease such as MT. Therefore taking a comparative proteomic approach to characterize the changes in the protein profile of MT vitreous may lead to the identification of potential biomarkers of this disease.
Vitreous samples were prepared for proteome analysis by depleting human serum albumin and then subsequently digesting the depleted sample with trypsin. Tryptically digested peptides were labelled with isobaric mass spectrometry (MS) based quantitative tags, iTRAQ (Applied Biosystems, CA, USA), analysed using nano LC MS/MS, and relative protein quantification obtained using Protein Pilot software (Applied Biosystems).
A total of 34 proteins were identified to be significantly differentially expressed, 19 and 25 of which were higher and lower in copy number, respectively, from MT vitreous. Some of those that were identified to have higher expression were vimentin, glial fibrillary acidic protein (GFAP), tubulin alpha-ubiquitous chain, and cellular retinoic acid binding protein I (CRABP I).
Since the vitreous apposes the retina it can provide a strong insight into the changes in biomolecular content such as proteins in the retina during disease. The application of highly sensitive quantitative proteomics technology to MT vitreous can provide this on a global level as well as information on potential mechanisms involved with the pathogenesis of MT. The differential expression of GFAP and vimentin indicate that the retinal glia, in particular Müller cells, may contribute to the disease process. While the identification of tubulin alpha-ubiquitous chain, which is a gap junction trafficking and regulatory protein, supports the characterized breakdown of the blood retinal barrier. From these preliminary findings a better understanding at a molecular level of what proteins may be involved with the pathogenesis of this disease is gained.
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