Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy.

Diabetic retinopathy is the leading cause of new cases of legal blindness among adults in the developed countries. Approximately 40% of all people with diabetes have diabetic retinopathy and 5% of these have sight-threatening form. As the advanced stage, where there is a high risk for vision loss, can develop without any serious symptoms, sometimes it is hard to detect it. A non invasive method to detect biomarkers characteristic for diabetic retinopathy from the tear fluid was developed. Tear samples from diabetic patients with no retinopathy, non proliferative and proliferative stages of diabetic retinopathy were analyzed and the protein content of each sample was compared to the protein content of tear pool from healthy volunteers. The samples were labeled with iTRAQ fourplex labels and were analyzed with nanoHPLC coupled ESI-MS/MS mass spectrometry. The lipocalin 1, lactotransferrin, lacritin, lysozyme C, lipophilin A and immunoglobulin lambda chain were identified as possible biomarker candidates with significantly higher relative levels in the tear of patients with diabetic retinopathy.

[1]  F. Chew,et al.  Proteomic analysis of human tears: defensin expression after ocular surface surgery. , 2004, Journal of proteome research.

[2]  R. Beuerman,et al.  Detection of substance P in human tears by laser desorption mass spectrometry and immunoassay. , 1997, Current eye research.

[3]  J. Rivera,et al.  Proliferative retinopathies: angiogenesis that blinds. , 2010, The international journal of biochemistry & cell biology.

[4]  R. Sariri,et al.  Tear proteins in health, disease, and contact lens wear , 2008, Biochemistry (Moscow).

[5]  D. Tan,et al.  Analysis of rabbit tear proteins by high-pressure liquid chromatography/electrospray ionization mass spectrometry. , 2002, Rapid communications in mass spectrometry : RCM.

[6]  David Krumholz,et al.  Membrane array characterization of 80 chemokines, cytokines, and growth factors in open- and closed-eye tears: angiogenin and other defense system constituents. , 2005, Investigative ophthalmology & visual science.

[7]  N. J. Van Haeringen,et al.  Clinical biochemistry of tears , 1981 .

[8]  J. Tőzsér,et al.  Plasminogen activator inhibitor in human tears after laser refractive surgery , 2004, Journal of cataract and refractive surgery.

[9]  T. Colgan,et al.  Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. , 2005, Journal of proteome research.

[10]  F. Grus,et al.  Two‐dimensional analysis of tear protein patterns of diabetic patients , 2001, Electrophoresis.

[11]  A. Gooley,et al.  Establishment of the human reflex tear two‐dimensional polyacrylamide gel electrophoresis reference map: New proteins of potential diagnostic value , 1997, Electrophoresis.

[12]  Lei Zhou,et al.  Characterisation of human tear proteins using high-resolution mass spectrometry. , 2006, Annals of the Academy of Medicine, Singapore.

[13]  P N Dilly,et al.  Structure and function of the tear film. , 1994, Advances in experimental medicine and biology.

[14]  T. Tachikawa,et al.  Periostin, discovered by nano-flow liquid chromatography and mass spectrometry, is a novel marker of diabetic retinopathy. , 2010, Biochemical and biophysical research communications.

[15]  J. Mcgill,et al.  Normal tear protein profiles and age-related changes. , 1984, The British journal of ophthalmology.

[16]  J. Gimeno-Orna,et al.  Ability of retinopathy to predict cardiovascular disease in patients with type 2 diabetes mellitus. , 2009, The American journal of cardiology.

[17]  K. Parker,et al.  Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents*S , 2004, Molecular & Cellular Proteomics.

[18]  F. Chew,et al.  Elevation of human alpha-defensins and S100 calcium-binding proteins A8 and A9 in tear fluid of patients with pterygium. , 2009, Investigative ophthalmology & visual science.

[19]  Chan‐Wha Kim,et al.  Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis. , 2005, Journal of proteome research.

[20]  R. Henriksson,et al.  Dysregulated secretoglobin expression in human lung cancers. , 2003, Lung cancer.

[21]  B. Shi,et al.  Advanced glycation end product (AGE) modified proteins in tears of diabetic patients , 2010, Molecular vision.

[22]  K. Park,et al.  Verification of biomarkers for diabetic retinopathy by multiple reaction monitoring. , 2010, Journal of proteome research.

[23]  N. McNamara,et al.  The tear film and defense against infection. , 2002, Advances in experimental medicine and biology.

[24]  G. Karakiulakis,et al.  Vitreous and Serum Levels of Platelet-Derived Growth Factor and Their Correlation in Patients with Proliferative Diabetic Retinopathy , 2009, Current eye research.

[25]  F. Chew,et al.  Proteomic analysis of rabbit tear fluid: Defensin levels after an experimental corneal wound are correlated to wound closure , 2007, Proteomics.

[26]  N. Noy.  Retinoid-binding proteins: mediators of retinoid action. , 2000, The Biochemical journal.

[27]  Zhang Li,et al.  Serum Retinol-Binding Protein 4 Levels in Patients with Diabetic Retinopathy , 2010, The Journal of international medical research.

[28]  Nan Wang,et al.  Characterization of human tear proteome using multiple proteomic analysis techniques. , 2005, Journal of proteome research.

[29]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[30]  Xiaoming Chen,et al.  Tear Film Function in Type 2 Diabetic Patients with Retinopathy , 2008, Ophthalmologica.

[31]  M. Moschos,et al.  Quantitative determination of glycosaminoglycans in tears of diabetic patients , 2008, Clinical ophthalmology.

[32]  F. Ortega,et al.  LIPOPOLYSACCHARIDE-BINDING PROTEIN AND SOLUBLE CD14 IN THE VITREOUS FLUID OF PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY , 2010, Retina.

[33]  G. Laurie,et al.  Restricted epithelial proliferation by lacritin via PKCα-dependent NFAT and mTOR pathways , 2006, The Journal of cell biology.

[34]  Kai Bruns,et al.  SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye. , 2005, Investigative ophthalmology & visual science.

[35]  D R Flower,et al.  The lipocalin protein family: structure and function. , 1996, The Biochemical journal.

[36]  A. Kijlstra,et al.  SDS-Minigel electrophoresis of human tears. Effect of sample treatment on protein patterns. , 1991, Investigative ophthalmology & visual science.

[37]  Matthias Mann,et al.  Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors , 2006, Genome Biology.

[38]  A. Berta.  Collection of tear samples with or without stimulation. , 1983, American journal of ophthalmology.

[39]  Lei Zhou,et al.  Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics. , 2009, Journal of proteome research.

[40]  J. Jonas,et al.  Apelin in plasma and vitreous and in fibrovascular retinal membranes of patients with proliferative diabetic retinopathy. , 2010, Investigative ophthalmology & visual science.