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M. Valar Nila, T. P. Vignesh, V. R. Muthukkaruppan, K. Dharmalingam; Evaluation of Haptoglobin and Its Isoforms as Plasma/Serum Biomarker for Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5088.
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© ARVO (1962-2015); The Authors (2016-present)
This study aims at the identification of post translational modifications of proteins in Diabetic Retinopathy (DR) patients and the validation of these putative biomarkers for early diagnosis and progression of Non-Proliferative Diabetic Retinopathy (NPDR) to severe Proliferative Diabetic Retinopathy (PDR).
Thirty serum samples from PDR, NPDR, NDR (Diabetes without Retinopathy), and Normal age matched controls were examined, using Two Dimensional Polyacrylamide Gel Electrophoresis (2D PAGE) to view the complete protein profile and to analyze the Haptoglobin expression and isoform changes, followed by MALDI TOF and Nano LC MS/MS based identification and quantification of differentially expressed proteins.
The protein profiling of the PDR sera differed from that of NDR, NPDR and controls. There is differential regulation of Haptoglobin isoforms in PDR patients. Interestingly, in Haptoglobin α2 chain - isofrom α2M is significantly upregulated in PDR. Further, among the 56 identified proteins, Ceruloplasmin, Alpha-1B-glycoprotein precursor, Serotransferrin precursor, Ig mu chain C region, Isocitrate dehydrogenase, Apolipoprotein A-IV precursor, Haptoglobin precursor were upregulated and Haemoglobin alpha chain, Haemoglobin beta chain, Albumin Isoform were downregulated in PDR serum.
Serum proteomic approaches prove to be useful in the investigation of disease pathogenesis. Most of the upregulated proteins are associated with the disease progression, thereby giving fundamental information for further research. In humans the genetic polymorphism of Haptoglobin 2-2 phenotype was shown to be associated with the prevalence and microvascular complications, in both the types of Diabetes Mellitus (DM). Based on our results, we propose that the analysis of Haptoglobin expression and isoform changes and also analysis of post translational modification of other serum proteins, will allow us to uncover a biomarker for early diagnosis and disease progression.
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