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A number of inherited and age-related eye diseases are caused by polymorphisms\/mutations or abnormal expression of proteases including serine proteases, cysteine proteases, and matrix metalloproteinases, amongst others. However, neither conventional genomic, transcriptomic, nor traditional proteomic profiling directly interrogate protease activities. Thus, leveraging ABPP to probe the activity of these enzyme classes as they relate to normal function and pathophysiology of the eye represents a unique potential opportunity for disease interrogation and possibly intervention.<\/jats:p>","DOI":"10.3390\/ijms20163855","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T11:05:32Z","timestamp":1565262332000},"page":"3855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prospective Application of Activity-Based Proteomic Profiling in Vision Research-Potential Unique Insights into Ocular Protease Biology and Pathology"],"prefix":"10.3390","volume":"20","author":[{"given":"Hui","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9057, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Hulleman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9057, USA"},{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/elps.11501601185","article-title":"Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium","volume":"16","author":"Wasinger","year":"1995","journal-title":"Electrophoresis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"M111.013722","DOI":"10.1074\/mcp.M111.013722","article-title":"System-wide perturbation analysis with nearly complete coverage of the yeast proteome by single-shot ultra HPLC runs on a bench top Orbitrap","volume":"11","author":"Nagaraj","year":"2012","journal-title":"Mol. Cell. Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/nature11835","article-title":"A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis","volume":"494","author":"Picotti","year":"2013","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.cell.2010.12.001","article-title":"A tissue-specific atlas of mouse protein phosphorylation and expression","volume":"143","author":"Huttlin","year":"2010","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature13302","article-title":"A draft map of the human proteome","volume":"509","author":"Kim","year":"2014","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nature12531","article-title":"Transcriptome and genome sequencing uncovers functional variation in humans","volume":"501","author":"Lappalainen","year":"2013","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/35015709","article-title":"Proteomics to study genes and genomes","volume":"405","author":"Pandey","year":"2000","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nature06525","article-title":"The biological impact of mass-spectrometry-based proteomics","volume":"450","author":"Cravatt","year":"2007","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1039\/c2cs15331a","article-title":"Mass spectrometry-based proteomics: Existing capabilities and future directions","volume":"41","author":"Angel","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cbpa.2008.07.024","article-title":"Mass spectrometry for proteomics","volume":"12","author":"Han","year":"2008","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0929-7855(95)00012-F","article-title":"Cytosolic phospholipase A2","volume":"12","author":"Clark","year":"1995","journal-title":"J. Lipid Mediat. Cell Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000468621","article-title":"Plasminogen activators and matrix metalloproteinases in angiogenesis","volume":"49","author":"Mignatti","year":"1996","journal-title":"Enzym. Protein"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev-biochem-060713-035352","article-title":"Activity-based profiling of proteases","volume":"83","author":"Sanman","year":"2014","journal-title":"Annu. Rev. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/nrc2901","article-title":"Activity-based protein profiling for biochemical pathway discovery in cancer","volume":"10","author":"Nomura","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10335","DOI":"10.1073\/pnas.162187599","article-title":"Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness","volume":"99","author":"Jessani","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","unstructured":"Llombart-Bosch, A., and Felipo, V. (2003). Proteomic Approaches to the Diagnosis, Treatment, and Monitoring of Cancer. New Trends in Cancer for the 21st Century: Proceedings of the International Symposium on Cancer: New Trends in Cancer for the 21st Century, held November 10\u201313, 2002, in Valencia, Spain, Springer."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1023\/B:NERE.0000023618.35579.7c","article-title":"Neuroproteomics: Expression profiling of the brain\u2019s proteomes in health and disease","volume":"29","author":"Kim","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6271","DOI":"10.1021\/ja901304n","article-title":"\u03b2-Lactam Probes as Selective Chemical-Proteomic Tools for the Identification and Functional Characterization of Resistance Associated Enzymes in MRSA","volume":"131","author":"Staub","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1021\/pr900788a","article-title":"Activity-based proteome profiling of hepatoma cells during hepatitis C virus replication using protease substrate probes","volume":"9","author":"Blais","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/prca.201470024","article-title":"Proteomics and the eye","volume":"8","author":"Semba","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R72","DOI":"10.1186\/gb-2006-7-8-r72","article-title":"Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors","volume":"7","author":"Mann","year":"2006","journal-title":"Genome Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1021\/pr300358k","article-title":"Human cornea proteome: Identification and quantitation of the proteins of the three main layers including epithelium, stroma, and endothelium","volume":"11","author":"Dyrlund","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1021\/pr500252r","article-title":"Proteomics of Fuchs\u2019 Endothelial Corneal Dystrophy Support That the Extracellular Matrix of Descemet\u2019s Membrane Is Disordered","volume":"13","author":"Poulsen","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_25","first-page":"1117","article-title":"Expression of degradative enzymes and protease inhibitors in corneas with keratoconus","volume":"39","author":"Zhou","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","first-page":"3299","article-title":"Elevated Levels of Proteolytic Enzymes in the Aging Human Vitreous","volume":"41","author":"Gilbert","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8412","DOI":"10.1038\/s41598-017-08688-2","article-title":"Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin","volume":"7","author":"Gupta","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/bdrc.20063","article-title":"Proteases in eye development and disease","volume":"78","author":"Wride","year":"2006","journal-title":"Birth Defects Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R59","DOI":"10.1093\/hmg\/ddt396","article-title":"Advances in the genomics of common eye diseases","volume":"22","author":"Sobrin","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1146\/annurev.biochem.75.101304.124125","article-title":"Activity-based protein profiling: From enzyme chemistry to proteomic chemistry","volume":"77","author":"Cravatt","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14694","DOI":"10.1073\/pnas.96.26.14694","article-title":"Activity-based protein profiling: The serine hydrolases","volume":"96","author":"Liu","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10000","DOI":"10.1073\/pnas.0402784101","article-title":"Activity-based probes for the proteomic profiling of metalloproteases","volume":"101","author":"Saghatelian","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14435","DOI":"10.1021\/ja047044i","article-title":"Developing Photoactive Affinity Probes for Proteomic Profiling:\u2009 Hydroxamate-based Probes for Metalloproteases","volume":"126","author":"Chan","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1126\/science.1070925","article-title":"Identification of signal peptide peptidase, a presenilin-type aspartic protease","volume":"296","author":"Weihofen","year":"2002","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1586\/14789450.5.5.721","article-title":"Activity-based probes as a tool for functional proteomic analysis of proteases","volume":"5","author":"Fonovic","year":"2008","journal-title":"Expert Rev. Proteom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S1074-5521(02)00238-7","article-title":"Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design","volume":"9","author":"Greenbaum","year":"2002","journal-title":"Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/nprot.2007.194","article-title":"Tandem orthogonal proteolysis-activity-based protein profiling (TOP-ABPP)--a general method for mapping sites of probe modification in proteomes","volume":"2","author":"Weerapana","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1002\/anie.200603811","article-title":"A mild chemically cleavable linker system for functional proteomic applications","volume":"46","author":"Verhelst","year":"2007","journal-title":"Angew. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30433","DOI":"10.1074\/jbc.R800035200","article-title":"Proteases: Multifunctional Enzymes in Life and Disease","volume":"283","author":"Bond","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1096\/fj.06-7924com","article-title":"Cathepsin cysteine proteases in cardiovascular disease","volume":"21","author":"Lutgens","year":"2007","journal-title":"Faseb J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1152\/physrev.00023.2009","article-title":"Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process","volume":"90","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1182\/blood-2010-01-257287","article-title":"Mast cell proteases: Multifaceted regulators of inflammatory disease","volume":"115","author":"Pejler","year":"2010","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/ng1750","article-title":"Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration","volume":"38","author":"Gold","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/ejhg.2008.140","article-title":"Variation near complement factor I is associated with risk of advanced AMD","volume":"17","author":"Fagerness","year":"2009","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molimm.2016.11.016","article-title":"The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment","volume":"84","author":"Geerlings","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1073\/pnas.0812584106","article-title":"Functional basis of protection against age-related macular degeneration conferred by a common polymorphism in complement factor B","volume":"106","author":"Montes","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1073\/pnas.1019338108","article-title":"Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk","volume":"108","author":"Heurich","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3109\/13816810.2013.766217","article-title":"Complement factor B polymorphism and the phenotype of early age-related macular degeneration","volume":"35","author":"Mantel","year":"2014","journal-title":"Ophthalmic Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/hmg\/ddp472","article-title":"Genetic control of the alternative pathway of complement in humans and age-related macular degeneration","volume":"19","author":"Hecker","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1167\/iovs.09-3928","article-title":"Plasma complement components and activation fragments: Associations with age-related macular degeneration genotypes and phenotypes","volume":"50","author":"Reynolds","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6628","DOI":"10.1167\/iovs.12-9587","article-title":"Activation of the alternative complement pathway in vitreous is controlled by genetics in age-related macular degeneration","volume":"53","author":"Loyet","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12839","DOI":"10.1073\/pnas.1102167108","article-title":"Structural basis for complement factor I control and its disease-associated sequence polymorphisms","volume":"108","author":"Roversi","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/ng.2640","article-title":"A functional variant in the CFI gene confers a high risk of age-related macular degeneration","volume":"45","author":"Nilsson","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/ng.2578","article-title":"Seven new loci associated with age-related macular degeneration","volume":"45","author":"Fritsche","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_55","first-page":"1253","article-title":"Complement factor I and age-related macular degeneration","volume":"20","author":"Alexander","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/ng.2741","article-title":"Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration","volume":"45","author":"Seddon","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1167\/iovs.16-20867","article-title":"Systematic Functional Testing of Rare Variants: Contributions of CFI to Age-Related Macular DegenerationFunctional Rare Variants in CFI Contribute to AMD","volume":"58","author":"Tan","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","first-page":"3861","article-title":"Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels","volume":"24","author":"Kavanagh","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_59","first-page":"2273","article-title":"Lack of association of CFD polymorphisms with advanced age-related macular degeneration","volume":"16","author":"Zeng","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8828","DOI":"10.1167\/iovs.11-7933","article-title":"Complement factor D in age-related macular degeneration","volume":"52","author":"Stanton","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1126\/science.1133807","article-title":"HTRA1 promoter polymorphism in wet age-related macular degeneration","volume":"314","author":"Dewan","year":"2006","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1126\/science.1133811","article-title":"A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration","volume":"314","author":"Yang","year":"2006","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.ophtha.2007.10.032","article-title":"Alleles in the HtrA serine peptidase 1 gene alter the risk of neovascular age-related macular degeneration","volume":"115","author":"Deangelis","year":"2008","journal-title":"Ophthalmology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/nrm3065","article-title":"HTRA proteases: Regulated proteolysis in protein quality control","volume":"12","author":"Clausen","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1517\/14728222.2010.487867","article-title":"HtrA proteins as targets in therapy of cancer and other diseases","volume":"14","author":"Lipinska","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_66","first-page":"92","article-title":"Human HtrA1 in the archived eyes with age-related macular degeneration","volume":"105","author":"Chan","year":"2007","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e12710","DOI":"10.1111\/acel.12710","article-title":"HTRA1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1","volume":"17","author":"Lin","year":"2018","journal-title":"Aging Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14578","DOI":"10.1073\/pnas.1102853108","article-title":"Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice","volume":"108","author":"Jones","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1016\/j.ajpath.2018.08.012","article-title":"High-Temperature Requirement A 1 Causes Photoreceptor Cell Death in Zebrafish Disease Models","volume":"188","author":"Oura","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1042\/CS20130463","article-title":"PEDF and its roles in physiological and pathological conditions: Implication in diabetic and hypoxia-induced angiogenic diseases","volume":"128","author":"He","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.exer.2016.10.017","article-title":"Mapping wild-type and R345W fibulin-3 intracellular interactomes","volume":"153","author":"Hulleman","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1080\/02713689808951215","article-title":"Identification, origins and the diurnal role of the principal serine protease inhibitors in human tear fluid","volume":"17","author":"Sathe","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1128\/MMBR.64.4.821-846.2000","article-title":"Proteases for Cell Suicide: Functions and Regulation of Caspases","volume":"64","author":"Chang","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/cdd.2014.216","article-title":"Old, new and emerging functions of caspases","volume":"22","author":"Shalini","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"a008656","DOI":"10.1101\/cshperspect.a008656","article-title":"Caspase functions in cell death and disease","volume":"5","author":"McIlwain","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17032","DOI":"10.1038\/cddiscovery.2017.32","article-title":"Caspases in retinal ganglion cell death and axon regeneration","volume":"3","author":"Thomas","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.1167\/iovs.18-24045","article-title":"Caspase-2 Mediates Site-Specific Retinal Ganglion Cell Death After Blunt Ocular InjuryCaspase-2 in Blunt Ocular Injury","volume":"59","author":"Thomas","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1167\/iovs.02-0492","article-title":"Caspase Activation in an Experimental Model of Retinal Detachment","volume":"44","author":"Zacks","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-015-0039-2","article-title":"Caspase-7: A critical mediator of optic nerve injury-induced retinal ganglion cell death","volume":"10","author":"Choudhury","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.2337\/diabetes.51.4.1172","article-title":"Caspase Activation in Retinas of Diabetic and Galactosemic Mice and Diabetic Patients","volume":"51","author":"Mohr","year":"2002","journal-title":"Diabetes"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"31240","DOI":"10.1074\/jbc.M502641200","article-title":"Involvement of inflammation, degradation, and apoptosis in a mouse model of glaucoma","volume":"280","author":"Zhou","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_82","first-page":"1077","article-title":"Caspase Activation and Amyloid Precursor Protein Cleavage in Rat Ocular Hypertension","volume":"43","author":"McKinnon","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e173","DOI":"10.1038\/cddis.2011.54","article-title":"Ocular neuroprotection by siRNA targeting caspase-2","volume":"2","author":"Ahmed","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10494","DOI":"10.1523\/JNEUROSCI.0148-11.2011","article-title":"Involvement of Caspase-6 and Caspase-8 in Neuronal Apoptosis and the Regenerative Failure of Injured Retinal Ganglion Cells","volume":"31","author":"Monnier","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1155\/2014\/417986","article-title":"Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema","volume":"2014","author":"Beasley","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nm.4450","article-title":"cGAS drives noncanonical-inflammasome activation in age-related macular degeneration","volume":"24","author":"Kerur","year":"2018","journal-title":"Nat. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/mt.2015.30","article-title":"Gene Therapy With the Caspase Activation and Recruitment Domain Reduces the Ocular Inflammatory Response","volume":"23","author":"Ildefonso","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_88","first-page":"65","article-title":"Role of calpain in apoptosis","volume":"13","author":"Momeni","year":"2011","journal-title":"Cell J."},{"key":"ref_89","first-page":"e218","article-title":"Role of Calpain in Pathogenesis of Human Disease Processes","volume":"2","author":"Potz","year":"2016","journal-title":"J. Nat. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/S1357-2725(02)00009-2","article-title":"Calpain","volume":"34","author":"Perrin","year":"2002","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1167\/iovs.09-4364","article-title":"Calpain Activation in Experimental Glaucoma","volume":"51","author":"Huang","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.1167\/iovs.11-7497","article-title":"Calpain, not caspase, is the causative protease for hypoxic damage in cultured monkey retinal cells","volume":"52","author":"Nakajima","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Hoang, M.V., Nagy, J.A., Fox, J.E., and Senger, D.R. (2010). Moderation of calpain activity promotes neovascular integration and lumen formation during VEGF-induced pathological angiogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013612"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.bbadis.2010.08.008","article-title":"Calpain inhibitors reduce retinal hypoxia in ischemic retinopathy by improving neovascular architecture and functional perfusion","volume":"1812","author":"Hoang","year":"2011","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ajo.2016.04.009","article-title":"Calpain and Caspase-12 Expression in Lens Epithelial Cells of Diabetic Cataracts","volume":"167","author":"Ahn","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.exer.2006.05.017","article-title":"The role of cathepsins in ocular physiology and pathology","volume":"84","author":"Im","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S0167-4838(99)00263-0","article-title":"Lysosomal cysteine proteases: More than scavengers","volume":"1477","author":"Turk","year":"2000","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0014-4835(03)00148-9","article-title":"Involvement of corneal nerves in the progression of keratoconus","volume":"77","author":"Brookes","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1006\/exer.2001.1157","article-title":"Cellular incursion into Bowman\u2019s membrane in the peripheral cone of the keratoconic cornea","volume":"74","author":"Sherwin","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1167\/iovs.04-0549","article-title":"Increased levels of catalase and cathepsin V\/L2 but decreased TIMP-1 in keratoconus corneas: Evidence that oxidative stress plays a role in this disorder","volume":"46","author":"Kenney","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.exer.2006.03.009","article-title":"Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium\/choroid of the mouse","volume":"83","author":"Alizadeh","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0304-3940(97)00946-4","article-title":"Cathepsin E immunoreactivity in human ocular tissues: Influence of aging and pathological states","volume":"240","author":"Bernstein","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0940-9602(11)80123-8","article-title":"Localization of cathepsin D in rat ocular tissues. An immunohistochemical study","volume":"177","year":"1995","journal-title":"Ann. Anat."},{"key":"ref_104","first-page":"580","article-title":"The use of adenovirus-mediated gene transfer to develop a rat model for photoreceptor degeneration","volume":"41","author":"Lai","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1136\/bjo.86.2.214","article-title":"CST3 genotype associated with exudative age related macular degeneration","volume":"86","author":"Zurdel","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Nguyen, A., and Hulleman, J.D. (2016). Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147684"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1183\/09031936.00146510","article-title":"Biological role of matrix metalloproteinases: A critical balance","volume":"38","author":"Schilling","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.cardiores.2005.12.002","article-title":"Structure and function of matrix metalloproteinases and TIMPs","volume":"69","author":"Nagase","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbamcr.2010.01.003","article-title":"The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity","volume":"1803","author":"Brew","year":"2010","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_110","first-page":"1308","article-title":"Metalloproteinases as mediators of inflammation and the eyes: Molecular genetic underpinnings governing ocular pathophysiology","volume":"10","author":"Singh","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.12659\/MSM.889887","article-title":"Age-related macular degeneration and changes in the extracellular matrix","volume":"20","author":"Nita","year":"2014","journal-title":"Med Sci. Monit."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1167\/iovs.10-6678","article-title":"Disturbed Matrix Metalloproteinase Activity of Bruch\u2019s Membrane in Age-Related Macular Degeneration","volume":"52","author":"Hussain","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/sj.eye.6702722x","article-title":"Plasma levels of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in age-related macular degeneration","volume":"22","author":"Chau","year":"2007","journal-title":"Eye"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/01.GIM.0000159903.69597.73","article-title":"MMP-9 microsatellite polymorphism and susceptibility to exudative form of age-related macular degeneration","volume":"7","author":"Fiotti","year":"2005","journal-title":"Genet. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1093\/aje\/kwn024","article-title":"Estrogen receptor alpha and matrix metalloproteinase 2 polymorphisms and age-related maculopathy in older women","volume":"167","author":"Seitzman","year":"2008","journal-title":"Am. J. Epidemiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1517\/13543784.2012.681043","article-title":"Matrix metalloproteinases in diabetic retinopathy: Potential role of MMP-9","volume":"21","author":"Kowluru","year":"2012","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_117","first-page":"498","article-title":"Retinal Neovascularization Is Suppressed With a Matrix Metalloproteinase Inhibitor","volume":"117","author":"Das","year":"1999","journal-title":"JAMA Ophthalmol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/labinvest.3700251","article-title":"Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier","volume":"85","author":"Giebel","year":"2005","journal-title":"Lab. Investig."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/labinvest.2010.89","article-title":"Matrix metalloproteinase-2 in the development of diabetic retinopathy and mitochondrial dysfunction","volume":"90","author":"Mohammad","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7756","DOI":"10.1167\/iovs.13-13088","article-title":"MMPs in the trabecular meshwork: Promising targets for future glaucoma therapies?","volume":"54","author":"Dekeyster","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1167\/iovs.02-0365","article-title":"Matrix Metalloproteinases and Their Inhibitors in Aqueous Humor of Patients with Pseudoexfoliation Syndrome\/Glaucoma and Primary Open-Angle Glaucoma","volume":"44","author":"Lommatzsch","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"BIO106","DOI":"10.1167\/iovs.17-21723","article-title":"Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients with GlaucomaMMPs in Tear Film in Glaucoma","volume":"58","author":"Sahay","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Wu, M.Y., Wu, Y., Zhang, Y., Liu, C.Y., Deng, C.Y., Peng, L., and Zhou, L. (2017). Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: A meta-analysis. BMC Ophthalmol., 17.","DOI":"10.1186\/s12886-017-0442-2"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/13816810.2013.838274","article-title":"The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration","volume":"36","author":"Liutkeviciene","year":"2015","journal-title":"Ophthalmic Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.neulet.2019.02.011","article-title":"gamma-Secretase and its modulators: Twenty years and beyond","volume":"701","author":"Xia","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_126","first-page":"41","article-title":"BACE-1 and gamma-Secretase as Therapeutic Targets for Alzheimer\u2019s Disease","volume":"12","author":"Maia","year":"2019","journal-title":"Pharm"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/978-3-319-17121-0_44","article-title":"A Non-Canonical Role for beta-Secretase in the Retina","volume":"854","author":"Qian","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1177\/0192623314553804","article-title":"Retinal Toxicity Induced by a Novel beta-secretase Inhibitor in the Sprague-Dawley Rat","volume":"43","author":"Fielden","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Pawlowska, E., Szczepanska, J., and Kaarniranta, K. (2019). Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010210"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1073\/pnas.1404059112","article-title":"Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract","volume":"112","author":"Liu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/B978-0-12-397863-9.00010-9","article-title":"Role of the ubiquitin-proteasome in protein quality control and signaling: Implication in the pathogenesis of eye diseases","volume":"109","author":"Shang","year":"2012","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.exer.2018.10.011","article-title":"Proteome-transcriptome analysis and proteome remodeling in mouse lens epithelium and fibers","volume":"179","author":"Zhao","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jprot.2016.05.006","article-title":"Human tear proteomics and peptidomics in ophthalmology: Toward the translation of proteomic biomarkers into clinical practice","volume":"150","author":"Azkargorta","year":"2017","journal-title":"J. Proteom."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.exer.2018.10.006","article-title":"Investigation of the global protein content from healthy human tears","volume":"179","author":"Dor","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.exer.2018.08.016","article-title":"Comparative proteomic analysis of normal and gliotic PVR retina and contribution of Muller glia to this profile","volume":"177","author":"Eastlake","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1038\/s41598-017-13817-y","article-title":"Proteomic analysis of human lacrimal and tear fluid in dry eye disease","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1559-0275-11-29","article-title":"Proteomic analysis of human vitreous humor","volume":"11","author":"Murthy","year":"2014","journal-title":"Clin. Proteom."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"Amd31","DOI":"10.1167\/iovs.18-24122","article-title":"The Proteomic Landscape in the Vitreous of Patients With Age-Related and Diabetic Retinal Disease","volume":"59","author":"Schori","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.acc.2018.05.005","article-title":"The Proteome of Cataract Markers: Focus on Crystallins","volume":"86","author":"Zhang","year":"2018","journal-title":"Adv. Clin. Chem."},{"key":"ref_140","first-page":"871","article-title":"Technical Brief: A novel strategy for enrichment of trabecular meshwork protease proteome","volume":"14","author":"Picciani","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1021\/acs.jmedchem.5b00449","article-title":"Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization","volume":"58","author":"Basavarajappa","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"25509","DOI":"10.1038\/srep25509","article-title":"A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy","volume":"6","author":"Sulaiman","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1021\/acschembio.7b00854","article-title":"Chemical Proteomics Reveals Soluble Epoxide Hydrolase as a Therapeutic Target for Ocular Neovascularization","volume":"13","author":"Sulaiman","year":"2018","journal-title":"ACS Chem. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:09:30Z","timestamp":1760188170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,8]]},"references-count":143,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20163855"],"URL":"https:\/\/doi.org\/10.3390\/ijms20163855","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,8]]}}}