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Proteomic analysis of human serum from diabetic retinopathy.

ABSTRACT: AIM:To establish and compare serum proteomic of diabetic retinopathy (DR) patients in various phases and discuss pathogenesis of DR so as to find out possible serum specific molecular markers for early diagnosis of DR. METHODS:Thirty-two subjects were divided into four groups: one group of eight type 2 diabetes mellitus (T2DM) patients without apparent DR (No-DR, NDR), one group of eight T2DM patients with non-proliferative diabetic retinopathy (NPDR), one group of eight T2DM patients with proliferative diabetic retinopathy (PDR) and one group of eight healthy volunteer participants. Two dimensional fluorescence difference gel electrophoresis (2D-DIGE) was applied to establish differential protein expression profiles in four groups. Matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-TOF MS) was applied to identify mass spectrometry of differential proteins and analyze follow-up bioinformatics. RESULTS:2D-DIGE maps of serum protein were satisfactory obtained from NDR, NPDR, PDR and normal control groups. Twenty-six different proteins spots were screened (the volume ratio was >1.5 based on DeCyder software analysis). Twenty-four of them were verified and two of them were not. Fifteen proteins were verified. Most of them were high-abundant proteins in serum. The four relatively low-abundant ones were beta 2-glycoprotein I (?(2)-GPI), alpha2-HS-glycoprotein(AHSG), alpha1-acid glycoprotein(?(1)-AGP) and apolipoprotein A-1(apo A-1). ?(2)-GPI expression was gradually increased in the development of DR but unrelated to the severity of DR. The volume ratio of ?(2)-GPI is 1.54, 2.43, and 2.84 in NDR, NPDR and PDR group respectively compared with normal control group. CONCLUSION:Serum proteomic analysis of 2D-DIGE combined with MALDI-TOF-TOF MS is feasible to be applied in the study of DR. ?(2)-GPI probably takes part in the process of DR occurrence and development and it could be a candidate biomarker on DR diagnosis in early phase.

SUBMITTER: Liu YP

PROVIDER: S-EPMC3340797 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Proteomic analysis of human serum from diabetic retinopathy.

Liu Yin-Ping YP Hu Shui-Wang SW Wu Zhen-Feng ZF Mei Li-Xin LX Lang Ping P Lu Xiao-He XH

International journal of ophthalmology 20111218 6

<h4>Aim</h4>To establish and compare serum proteomic of diabetic retinopathy (DR) patients in various phases and discuss pathogenesis of DR so as to find out possible serum specific molecular markers for early diagnosis of DR.<h4>Methods</h4>Thirty-two subjects were divided into four groups: one group of eight type 2 diabetes mellitus (T2DM) patients without apparent DR (No-DR, NDR), one group of eight T2DM patients with non-proliferative diabetic retinopathy (NPDR), one group of eight T2DM pati ...[more]

PMID: 22553731

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Project description:PurposeUsing previously approved medications for new indications can expedite the lengthy and expensive drug development process. We describe a bioinformatics pipeline that integrates genomics and proteomics platforms to identify already-approved drugs that might be useful to treat diabetic retinopathy (DR).MethodsProteomics analysis of vitreous humor samples from 12 patients undergoing pars plana vitrectomy for DR and a whole genome dataset (UKBiobank TOPMed-imputed) from 1330 individuals with DR and 395,155 controls were analyzed independently to identify biological pathways associated with DR. Common biological pathways shared between both datasets were further analyzed (STRING and REACTOME analyses) to identify target proteins for probable drug modulation. Curated target proteins were subsequently analyzed by the BindingDB database to identify chemical compounds they interact with. Identified chemical compounds were further curated through the Expasy SwissSimilarity database for already-approved drugs that interact with target proteins.ResultsThe pathways in each dataset (proteomics and genomics) converged in the upregulation of a previously unknown pathway involved in DR (RUNX2 signaling; constituents MMP-13 and LGALS3), with an emphasis on its role in angiogenesis and blood-retina barrier. Bioinformatics analysis identified U.S. Food and Drug Administration (FDA)-approved medications (raltitrexed, pemetrexed, glyburide, probenecid, clindamycin hydrochloride, and ticagrelor) that, in theory, may modulate this pathway.ConclusionsThe bioinformatics pipeline described here identifies FDA-approved drugs that can be used for new alternative indications. These theoretical candidate drugs should be validated with experimental studies.Translational relevanceOur study suggests possible drugs for DR treatment based on an integrated proteomics and genomics pipeline. This approach can potentially expedite the drug discovery process by identifying already-approved drugs that might be used for new indications.

Project description:IntroductionFew qualitative studies have explored the patient experience of daily life with proliferative diabetic retinopathy (PDR) and associated treatments. Herein, a conceptual model was developed to comprehensively examine symptoms, functional impacts, and treatment experiences in PDR.MethodsA qualitative, mixed-methods study comprising a literature search and semi-structured interviews with clinicians and patients was conducted. Published literature and online patient resources were searched to identify concepts relevant to patients, including symptoms, functional impacts, and treatment experiences of PDR. Semi-structured interviews with experienced clinicians were conducted to identify symptoms and impacts reported by patients with PDR and to receive feedback regarding concepts identified from the literature search. A preliminary conceptual model was then developed based on findings from the literature search and clinician interviews. Patients with PDR participated in two rounds of semi-structured interviews to identify additional concepts relevant to the patient experience in PDR and associated treatments, which informed revisions to the conceptual model. Saturation of patient interviews was assessed.ResultsFindings from the literature search and clinician interviews yielded 109 concepts that were included in a preliminary conceptual model with three overarching domains: symptoms, impacts, and managing the disease. Clinicians confirmed concepts identified from the literature search. During interviews, patients reported a broad spectrum of symptoms (e.g., red vision); functional impacts relating to activities of daily living (e.g., reading), emotional functioning (e.g., loss of independence), and social functioning (e.g., problems recognizing faces); and treatment experiences (e.g., improves eye problems, no change) associated with PDR. Additional concepts elicited in patient interviews informed revisions to the conceptual model. Saturation was achieved in the patient sample.ConclusionsA wide variety of symptoms, functional impacts, and treatment experiences that significantly affect health-related quality of life were identified in patients with PDR. These insights are critical for understanding PDR symptomology and assessing treatment response.

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Proteomic analysis of human serum from diabetic retinopathy.

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Proteomic analysis of human serum from diabetic retinopathy.

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