The Human Eye Proteome Project: Perspectives on an emerging proteome

There are an estimated 285 million people with visual impairment worldwide, of whom 39 million are blind. The pathogenesis of many eye diseases remains poorly understood. The human eye is currently an emerging proteome that may provide key insight into the biological pathways of disease. We review proteomic investigations of the human eye and present a catalogue of 4842 nonredundant proteins identified in human eye tissues and biofluids to date. We highlight the need to identify new biomarkers for eye diseases using proteomics. Recent advances in proteomics do now allow the identification of hundreds to thousands of proteins in tissues and fluids, characterization of various PTMs and simultaneous quantification of multiple proteins. To facilitate proteomic studies of the eye, the Human Eye Proteome Project (HEPP) was organized in September 2012. The HEPP is one of the most recent components of the Biology/Disease‐driven Human Proteome Project (B/D‐HPP) whose overarching goal is to support the broad application of state‐of‐the‐art measurements of proteins and proteomes by life scientists studying the molecular mechanisms of biological processes and human disease. The large repertoire of investigative proteomic tools has great potential to transform vision science and enhance understanding of physiology and disease processes that affect sight.

[1]  Laxmikanth Kankipati,et al.  Vascular changes in the retina of hypoxic neonatal rats , 2013 .

[2]  Gary D Bader,et al.  The biology/disease-driven human proteome project (B/D-HPP): enabling protein research for the life sciences community. , 2013, Journal of proteome research.

[3]  J. V. Van Eyk,et al.  Analysis of protein isoforms: Can we do it better? , 2012, Proteomics.

[4]  Thomas F Dyrlund,et al.  MS Data Miner: A web‐based software tool to analyze, compare, and share mass spectrometry protein identifications , 2012, Proteomics.

[5]  K. Nichols,et al.  iTRAQ quantitative proteomics in the analysis of tears in dry eye patients. , 2012, Investigative ophthalmology & visual science.

[6]  Lei Zhou,et al.  In-depth analysis of the human tear proteome. , 2012, Journal of proteomics.

[7]  J. Kang,et al.  Proteomic analysis of the aqueous humor in age-related macular degeneration (AMD) patients. , 2012, Journal of proteome research.

[8]  K. Lamnissou,et al.  Biomarkers in primary open angle glaucoma , 2012, Clinical chemistry and laboratory medicine.

[9]  A. Izzotti,et al.  New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor. , 2012, Investigative ophthalmology & visual science.

[10]  M. Dharsee,et al.  Proteomics analyses of activated human optic nerve head lamina cribrosa cells following biomechanical strain. , 2012, Investigative ophthalmology & visual science.

[11]  J. Enghild,et al.  Human Cornea Proteome: Identification and Quantitation of the Proteins of the Three Main Layers Including Epithelium, Stroma, and Endothelium , 2012, Journal of proteome research.

[12]  J. Durán,et al.  Evaluation of inter-day and inter-individual variability of tear peptide/protein profiles by MALDI-TOF MS analyses , 2012, Molecular vision.

[13]  B. Holden,et al.  Differential Gel Electrophoresis of the Tear Proteome , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[14]  R. Aebersold,et al.  Selected reaction monitoring–based proteomics: workflows, potential, pitfalls and future directions , 2012, Nature Methods.

[15]  M. Washington,et al.  Precision of Multiple Reaction Monitoring Mass Spectrometry Analysis of Formalin-Fixed, Paraffin-Embedded Tissue , 2012, Journal of proteome research.

[16]  Alan Cruess,et al.  An estimation of the worldwide economic and health burden of visual impairment , 2012, Global public health.

[17]  Adrienne Csutak,et al.  Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy. , 2012, Journal of proteomics.

[18]  A. Urbani,et al.  Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma. , 2012, Molecular bioSystems.

[19]  F. Wang,et al.  Characterisation of the vitreous proteome in proliferative diabetic retinopathy , 2012, Proteome Science.

[20]  M. Dhaenens,et al.  In vivo relevance of citrullinated proteins and the challenges in their detection , 2012, Proteomics.

[21]  J. Enghild,et al.  Composition and proteolytic processing of corneal deposits associated with mutations in the TGFBI gene. , 2012, Experimental eye research.

[22]  Michael J. Sweredoski,et al.  Protein Interaction Profiling of the p97 Adaptor UBXD1 Points to a Role for the Complex in Modulating ERGIC-53 Trafficking* , 2012, Molecular & Cellular Proteomics.

[23]  J. Silberg,et al.  A transposase strategy for creating libraries of circularly permuted proteins , 2012, Nucleic acids research.

[24]  G. Hageman,et al.  Pilot application of iTRAQ to the retinal disease Macular Telangiectasia. , 2012, Journal of proteome research.

[25]  Ludovic C. Gillet,et al.  Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis* , 2012, Molecular & Cellular Proteomics.

[26]  M. Mann,et al.  Ultra High Resolution Linear Ion Trap Orbitrap Mass Spectrometer (Orbitrap Elite) Facilitates Top Down LC MS/MS and Versatile Peptide Fragmentation Modes* , 2011, Molecular & Cellular Proteomics.

[27]  L. Desjardins,et al.  Deeper in the human cornea proteome using nanoLC-Orbitrap MS/MS: An improvement for future studies on cornea homeostasis and pathophysiology. , 2011, Journal of proteomics.

[28]  Yang Zhang,et al.  Functional implications of structural predictions for alternative splice proteins expressed in Her2/neu-induced breast cancers. , 2011, Journal of proteome research.

[29]  N. Zachara,et al.  Defining the Heart and Cardiovascular O-GlcNAcome: A Review of Approaches and Methods , 2011, Circulation. Cardiovascular genetics.

[30]  D. Pascolini,et al.  Global estimates of visual impairment: 2010 , 2011, British Journal of Ophthalmology.

[31]  J. Sivak,et al.  Proteomics Analyses of Human Optic Nerve Head Astrocytes Following Biomechanical Strain* , 2011, Molecular & Cellular Proteomics.

[32]  The UniProt Consortium,et al.  Reorganizing the protein space at the Universal Protein Resource (UniProt) , 2011, Nucleic Acids Res..

[33]  Z. Kyselova Mass spectrometry-based proteomics approaches applied in cataract research. , 2011, Mass spectrometry reviews.

[34]  A. Vertegaal,et al.  Uncovering Ubiquitin and Ubiquitin-like Signaling Networks , 2011, Chemical reviews.

[35]  Xu Lin,et al.  Quantitative detection of single amino acid polymorphisms by targeted proteomics. , 2011, Journal of molecular cell biology.

[36]  R. Beuerman,et al.  Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication. , 2011, Investigative ophthalmology & visual science.

[37]  J. Durán,et al.  Changes in tear protein profile in keratoconus disease , 2011, Eye.

[38]  Xianyin Lai,et al.  Alterations in the aqueous humor proteome in patients with a glaucoma shunt device , 2011, Molecular vision.

[39]  R. Aebersold,et al.  A High-Confidence Human Plasma Proteome Reference Set with Estimated Concentrations in PeptideAtlas* , 2011, Molecular & Cellular Proteomics.

[40]  Mihaela E. Sardiu,et al.  Building Protein-Protein Interaction Networks with Proteomics and Informatics Tools* , 2011, The Journal of Biological Chemistry.

[41]  Ivana K. Kim,et al.  Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions , 2011, Seminars in ophthalmology.

[42]  P. Mitchell,et al.  A review and meta-analysis of the association between C-reactive protein and age-related macular degeneration. , 2011, Survey of ophthalmology.

[43]  R. Joseph,et al.  Differential epithelial and stromal protein profiles in keratoconus and normal human corneas. , 2011, Experimental eye research.

[44]  Coziana Ciurtin,et al.  NANO-LC MASS SPECTROMETRY PROTEOMIC TEAR SECRETION ANALYSIS IN PATIENTS WITH SECONDARY SJÖGREN'S SYNDROME , 2011 .

[45]  Zlatko Trajanoski,et al.  Proteomic analysis of human cataract aqueous humour: Comparison of one-dimensional gel LCMS with two-dimensional LCMS of unlabelled and iTRAQ®-labelled specimens. , 2011, Journal of proteomics.

[46]  B. Honoré,et al.  Attempting to distinguish between endogenous and contaminating cytokeratins in a corneal proteomic study , 2011, BMC ophthalmology.

[47]  Yu‐Ju Chen,et al.  Phosphoproteomics characterization of novel phosphorylated sites of lens proteins from normal and cataractous human eye lenses , 2011, Molecular vision.

[48]  J. Durán,et al.  Changes in Tear Protein Profile in Patients With Conjunctivochalasis , 2011, Cornea.

[49]  Ningli Wang,et al.  Proteomic analysis of aqueous humor from patients with primary open angle glaucoma , 2010, Molecular vision.

[50]  Jan Ellenberg,et al.  Fluorescence perturbation techniques to study mobility and molecular dynamics of proteins in live cells: FRAP, photoactivation, photoconversion, and FLIP. , 2010, Cold Spring Harbor protocols.

[51]  Yehia Mechref,et al.  Alterations in the aqueous humor proteome in patients with Fuchs endothelial corneal dystrophy , 2010, Molecular vision.

[52]  R. Beuerman,et al.  Association of tear proteins with Meibomian gland disease and dry eye symptoms , 2010, British Journal of Ophthalmology.

[53]  T. Sobrino,et al.  Proteomic analysis of the tear film in patients with keratoconus , 2010, Molecular vision.

[54]  J. Nichols,et al.  Tear proteomics in keratoconus , 2010, Molecular vision.

[55]  M. Fautsch,et al.  Proteome analysis of human aqueous humor. , 2010, Investigative ophthalmology & visual science.

[56]  C. Cartiglia,et al.  Proteome alterations in primary open angle glaucoma aqueous humor. , 2010, Journal of proteome research.

[57]  E. Campos,et al.  Tear proteomics in evaporative dry eye disease , 2010, Eye.

[58]  R. Simó,et al.  New Pathogenic Candidates for Diabetic Macular Edema Detected By Proteomic Analysis , 2010, Diabetes Care.

[59]  Juhua Yang,et al.  Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature , 2010, Molecular vision.

[60]  T. Thingholm,et al.  Strategies for quantitation of phosphoproteomic data , 2010, Expert review of proteomics.

[61]  R. Truscott,et al.  Age-dependent deamidation of lifelong proteins in the human lens. , 2010, Investigative ophthalmology & visual science.

[62]  David M. Rissin,et al.  Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations , 2010, Nature Biotechnology.

[63]  Adam Gordois,et al.  The global economic cost of visual impairment , 2010 .

[64]  J. Hollyfield,et al.  Quantitative Proteomics: Comparison of the Macular Bruch Membrane/Choroid Complex from Age-related Macular Degeneration and Normal Eyes , 2010, Molecular & Cellular Proteomics.

[65]  B. Bodaghi,et al.  Pooling aqueous humor samples: bias in 2D-LC-MS/MS strategy? , 2010, Journal of Proteome Research.

[66]  Ying Gao,et al.  Bioinformatics Applications Note Sequence Analysis Cd-hit Suite: a Web Server for Clustering and Comparing Biological Sequences , 2022 .

[67]  Mu Wang,et al.  Proteomic analysis of human aqueous humor using multidimensional protein identification technology , 2009, Molecular vision.

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

[69]  O. Alcázar,et al.  Proteomics Characterization of Cell Membrane Blebs in Human Retinal Pigment Epithelium Cells* , 2009, Molecular & Cellular Proteomics.

[70]  R. Klein,et al.  Inflammatory, Hemostatic, and Other Novel Biomarkers for Diabetic Retinopathy , 2009, Diabetes Care.

[71]  J. Buring,et al.  Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. , 2009, Archives of ophthalmology.

[72]  Heath C. Thomas,et al.  Protein Extraction of Formalin-fixed, Paraffin-embedded Tissue Enables Robust Proteomic Profiles by Mass Spectrometry , 2009, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[73]  Daniel C. Liebler,et al.  Equivalence of Protein Inventories Obtained from Formalin-fixed Paraffin-embedded and Frozen Tissue in Multidimensional Liquid Chromatography-Tandem Mass Spectrometry Shotgun Proteomic Analysis* , 2009, Molecular & Cellular Proteomics.

[74]  F. Grus,et al.  Proteomics in Autoimmune Thyroid Eye Disease , 2009, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[75]  U. Jurkunas,et al.  Colocalization of increased transforming growth factor-beta-induced protein (TGFBIp) and Clusterin in Fuchs endothelial corneal dystrophy. , 2009, Investigative ophthalmology & visual science.

[76]  J. Bena,et al.  Assessing Susceptibility to Age-related Macular Degeneration with Proteomic and Genomic Biomarkers* , 2009, Molecular & Cellular Proteomics.

[77]  R. Truscott,et al.  Proteomic analysis of the oxidation of cysteine residues in human age-related nuclear cataract lenses. , 2008, Biochimica et biophysica acta.

[78]  M. Tress,et al.  Proteomics studies confirm the presence of alternative protein isoforms on a large scale , 2008, Genome Biology.

[79]  R. Truscott,et al.  Proteome analysis of human foetal, aged and advanced nuclear cataract lenses , 2008, Proteomics. Clinical applications.

[80]  J. M. Chaves,et al.  Multi-crystallin complexes exist in the water-soluble high molecular weight protein fractions of aging normal and cataractous human lenses. , 2008, Experimental eye research.

[81]  N. Komori,et al.  Proteome profiling of vitreoretinal diseases by cluster analysis , 2008, Proteomics. Clinical applications.

[82]  N. Pfeiffer,et al.  Transthyretin and complex protein pattern in aqueous humor of patients with primary open-angle glaucoma , 2008, Molecular vision.

[83]  C. Nordgaard,et al.  Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. , 2008, Investigative ophthalmology & visual science.

[84]  N. Joyce,et al.  Decreased expression of peroxiredoxins in Fuchs' endothelial dystrophy. , 2008, Investigative ophthalmology & visual science.

[85]  R. Semba Handbook of Nutrition and Ophthalmology , 2008 .

[86]  S. Bhattacharya,et al.  Technical Brief: A novel strategy for enrichment of trabecular meshwork protease proteome , 2008, Molecular vision.

[87]  L. Aiello,et al.  Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. , 2008, Journal of proteome research.

[88]  C. Nordgaard,et al.  Human retinal pigment epithelium proteome changes in early diabetes , 2008, Diabetologia.

[89]  Kari B. Green-Church,et al.  Investigation of the human tear film proteome using multiple proteomic approaches , 2008, Molecular vision.

[90]  Ningli Wang,et al.  Proteomic analysis of aqueous humor from patients with myopia , 2008, Molecular vision.

[91]  K. Park,et al.  Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients , 2007, Proteomics.

[92]  Chunwei Zhang,et al.  Comparison of two tandem mass spectrometry-based methods for analyzing the proteome of healthy human lens fibers. , 2007, Molecular vision.

[93]  M. Kirk,et al.  Proteomic analysis of water insoluble proteins from normal and cataractous human lenses. , 2007, Molecular vision.

[94]  T. Wong,et al.  Management of diabetic retinopathy: a systematic review. , 2007, JAMA.

[95]  Christophe Baudouin,et al.  The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). , 2007, The ocular surface.

[96]  R. Simó,et al.  Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy , 2007, Diabetologia.

[97]  S. West Epidemiology of Cataract: Accomplishments over 25 years and Future Directions , 2007, Ophthalmic epidemiology.

[98]  R. Pfister,et al.  Molecular changes in selected epithelial proteins in human keratoconus corneas compared to normal corneas. , 2006, Molecular Vision.

[99]  I. Schwab,et al.  Trends of penetrating keratoplasty in the United States from 1980 to 2004. , 2006, Ophthalmology.

[100]  P A Pevzner,et al.  Age-related changes in human crystallins determined from comparative analysis of post-translational modifications in young and aged lens: does deamidation contribute to crystallin insolubility? , 2006, Journal of proteome research.

[101]  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.

[102]  C. Kannabiran,et al.  TGFBI gene mutations in corneal dystrophies , 2006, Human mutation.

[103]  C. Reilly,et al.  The proteome of central and peripheral retina with progression of age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[104]  S. Bhattacharya,et al.  Proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis. , 2006, Investigative ophthalmology & visual science.

[105]  C. Reilly,et al.  Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[106]  H. Quigley,et al.  The number of people with glaucoma worldwide in 2010 and 2020 , 2006, British Journal of Ophthalmology.

[107]  K. Birkenkamp-Demtröder,et al.  Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study. , 2006, Experimental eye research.

[108]  Kyong Soo Park,et al.  Differential Expression of Vitreous Proteins in Proliferative Diabetic Retinopathy , 2006, Current eye research.

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

[110]  J. Enghild,et al.  A Dataset of Human Cornea Proteins Identified by Peptide Mass Fingerprinting and Tandem Mass Spectrometry*S , 2005, Molecular & Cellular Proteomics.

[111]  M. Kamei,et al.  Proteomic analysis of vitreous from diabetic macular edema. , 2005, Experimental eye research.

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

[113]  Susumu Sugai,et al.  Diagnostic potential of tear proteomic patterns in Sjögren's syndrome. , 2005, Journal of proteome research.

[114]  A. Makarov,et al.  The Orbitrap: a new mass spectrometer. , 2005, Journal of mass spectrometry : JMS.

[115]  Y. Hathout,et al.  Metabolic labeling of human primary retinal pigment epithelial cells for accurate comparative proteomics. , 2005, Journal of Proteome Research.

[116]  B. Honoré,et al.  Proteomic analysis of aqueous humour from patients with acute corneal rejection. , 2005, Acta ophthalmologica Scandinavica.

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

[118]  O. Srivastava,et al.  Crystallins in water soluble-high molecular weight protein fractions and water insoluble protein fractions in aging and cataractous human lenses. , 2004, Molecular vision.

[119]  E. Birney,et al.  The International Protein Index: An integrated database for proteomics experiments , 2004, Proteomics.

[120]  P. Jong Prevalence of age-related macular degeneration in the United States. , 2004 .

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

[122]  A. Tsugita,et al.  Proteome Analysis of Human Vitreous Proteins* , 2003, Molecular & Cellular Proteomics.

[123]  J. Buring,et al.  Prevalence of dry eye syndrome among US women. , 2003, American journal of ophthalmology.

[124]  A. Shimizu,et al.  Catalogue of soluble proteins in human vitreous humor by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization mass spectrometry including seven angiogenesis-regulating factors. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[125]  S. Gygi,et al.  Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[126]  R. Klein,et al.  Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. , 2003, Ophthalmology.

[127]  O. Srivastava,et al.  Existence of deamidated alphaB-crystallin fragments in normal and cataractous human lenses. , 2003, Molecular vision.

[128]  Masaru Miyagi,et al.  Drusen proteome analysis: An approach to the etiology of age-related macular degeneration , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[129]  A. Shimizu,et al.  Catalogue of soluble proteins in the human vitreous humor: comparison between diabetic retinopathy and macular hole. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[130]  John I. Clark,et al.  Shotgun identification of protein modifications from protein complexes and lens tissue , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[131]  M. Mann,et al.  Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics* , 2002, Molecular & Cellular Proteomics.

[132]  R. Aebersold,et al.  Optimization of the isotope-coded affinity tag-labeling procedure for quantitative proteome analysis. , 2001, Analytical biochemistry.

[133]  A Hofman,et al.  Risk factors for age-related macular degeneration: Pooled findings from three continents. , 2001, Ophthalmology.

[134]  H. Quigley Number of people with glaucoma worldwide. , 1996, The British journal of ophthalmology.

[135]  W. M. Bourne,et al.  A 48-year clinical and epidemiologic study of keratoconus. , 1986, American journal of ophthalmology.

[136]  J. Heath,et al.  In situ click chemistry: from small molecule discovery to synthetic antibodies. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[137]  F. Alkuraya,et al.  Identification of differentially expressed proteins in the aqueous humor of primary congenital glaucoma. , 2011, Experimental eye research.

[138]  G. Hageman,et al.  Age-Related Macular Degeneration (AMD) , 2008 .

[139]  A. Ramé [Age-related macular degeneration]. , 2006, Revue de l'infirmiere.

[140]  E. Dalmasso,et al.  SELDI-TOF-MS ProteinChip Array Profiling of Tears from Patients with Dry Eye , 2005 .

[141]  Benita J. O’Colmain,et al.  Prevalence of age-related macular degeneration in the United States. , 2004, Archives of ophthalmology.

[142]  M. Srinivasan,et al.  Corneal blindness: a global perspective. , 2001, Bulletin of the World Health Organization.

[143]  T. Sano,et al.  [Diabetic retinopathy]. , 2001, Nihon rinsho. Japanese journal of clinical medicine.

[144]  S. West Looking forward to 20/20: a focus on the epidemiology of eye diseases. , 2000, Epidemiologic reviews.