{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:58Z","timestamp":1791928678254,"version":"4.3.4"},"reference-count":48,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"7","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2018,6,11]]},"DOI":"10.1167\/iovs.18-24367","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T19:22:29Z","timestamp":1532114549000},"page":"2977","source":"Crossref","is-referenced-by-count":46,"title":["Integrated Stress Response and Decreased ECM in Cultured Stromal Cells From Keratoconus Corneas"],"prefix":"10.1167","volume":"59","author":[{"given":"James W.","family":"Foster","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Shinde","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, NYU Langone Health, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri S.","family":"Soiberman","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gajanan","family":"Sathe","sequence":"additional","affiliation":[{"name":"Manipal Academy of Higher Education, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, NYU Langone Health, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Dauoud","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, NYU Langone Health, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert S.","family":"Jun","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukti","family":"Chakravarti","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"},{"name":"Department of Ophthalmology, NYU Langone Health, New York, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-59-7-2977-b01","doi-asserted-by":"crossref","unstructured":"Klintworth GK, Damms T. Corneal dystrophies and keratoconus. Curr Opin Ophthalmol. 1995; 6: 44\u201356.","DOI":"10.1097\/00055735-199508000-00009"},{"key":"i1552-5783-59-7-2977-b02","doi-asserted-by":"crossref","unstructured":"Chang H-YP, Chodosh J. The genetics of keratoconus. Semin Ophthalmol. 2013; 28: 275\u2013280.","DOI":"10.3109\/08820538.2013.825295"},{"key":"i1552-5783-59-7-2977-b03","doi-asserted-by":"crossref","unstructured":"Andreassen TT, Hjorth Simonsen A, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res. 1980; 31: 435\u2013441.","DOI":"10.1016\/S0014-4835(80)80027-3"},{"key":"i1552-5783-59-7-2977-b04","doi-asserted-by":"crossref","unstructured":"Edwards M, McGhee CN, Dean S. The genetics of keratoconus. Clin Experiment Ophthalmol. 2001; 29: 345\u2013351.","DOI":"10.1046\/j.1442-9071.2001.d01-16.x"},{"key":"i1552-5783-59-7-2977-b05","doi-asserted-by":"crossref","unstructured":"Wagner H, Barr JT, Zadnik K. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study: methods and findings to date. Contact Lens Anterior Eye J Br Contact Lens Assoc. 2007; 30: 223\u2013232.","DOI":"10.1016\/j.clae.2007.03.001"},{"key":"i1552-5783-59-7-2977-b06","doi-asserted-by":"crossref","unstructured":"Critchfield JW, Calandra AJ, Nesburn AB, Kenney MC. Keratoconus: I. Biochemical studies. Exp Eye Res. 1988; 46: 953\u2013963.","DOI":"10.1016\/S0014-4835(88)80047-2"},{"key":"i1552-5783-59-7-2977-b07","doi-asserted-by":"crossref","unstructured":"Maurice DM. The structure and transparency of the cornea. J Physiol. 1957; 136: 263\u2013286.","DOI":"10.1113\/jphysiol.1957.sp005758"},{"key":"i1552-5783-59-7-2977-b08","doi-asserted-by":"crossref","unstructured":"McCally RL, Farrell RA. Light scattering from cornea and corneal transparency. In: Noninvasive Diagnostic Techniques in Ophthalmology. Springer, New York, NY; 1990: 189\u2013210.","DOI":"10.1007\/978-1-4613-8896-8_12"},{"key":"i1552-5783-59-7-2977-b09","doi-asserted-by":"crossref","unstructured":"Hassell JR, Birk DE. The molecular basis of corneal transparency. Exp Eye Res. 2010; 91: 326\u2013335.","DOI":"10.1016\/j.exer.2010.06.021"},{"key":"i1552-5783-59-7-2977-b10","doi-asserted-by":"crossref","unstructured":"Birk DE, Fitch JM, Babiarz JP, Linsenmayer TF. Collagen type I and type V are present in the same fibril in the avian corneal stroma. J Cell Biol. 1988; 106: 999\u20131008.","DOI":"10.1083\/jcb.106.3.999"},{"key":"i1552-5783-59-7-2977-b11","doi-asserted-by":"crossref","unstructured":"Sun M, Chen S, Adams SM, et al. Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional regulation of structure and function in a corneal-stroma-specific Col5a1-null mouse model. J Cell Sci. 2011; 124: 4096\u20134105.","DOI":"10.1242\/jcs.091363"},{"key":"i1552-5783-59-7-2977-b12","doi-asserted-by":"crossref","unstructured":"Critchfield JW, Calandra AJ, Nesburn AB, Kenney MC. Keratoconus: I. Biochemical studies. Exp Eye Res. 1988; 46: 953\u2013963.","DOI":"10.1016\/S0014-4835(88)80047-2"},{"key":"i1552-5783-59-7-2977-b13","doi-asserted-by":"crossref","unstructured":"Fini ME, Yue BY, Sugar J. Collagenolytic\/gelatinolytic metalloproteinases in normal and keratoconus corneas. Curr Eye Res. 1992; 11: 849\u2013862.","DOI":"10.3109\/02713689209033483"},{"key":"i1552-5783-59-7-2977-b14","doi-asserted-by":"crossref","unstructured":"Yue BY, Sugar J, Benveniste K. Heterogeneity in keratoconus: possible biochemical basis. Proc Soc Exp Biol Med. 1984; 175: 336\u2013341.","DOI":"10.3181\/00379727-175-41804"},{"key":"i1552-5783-59-7-2977-b15","doi-asserted-by":"crossref","unstructured":"Kenney MC, Chwa M, Opbroek AJ, Brown DJ. Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2\/tissue inhibitor of metalloproteinase ratio. Cornea. 1994; 13: 114\u2013124.","DOI":"10.1097\/00003226-199403000-00003"},{"key":"i1552-5783-59-7-2977-b16","doi-asserted-by":"crossref","unstructured":"Efron N, Hollingsworth JG. New perspectives on keratoconus as revealed by corneal confocal microscopy. Clin Exp Optom. 2008; 91: 34\u201355.","DOI":"10.1111\/j.1444-0938.2007.00195.x"},{"key":"i1552-5783-59-7-2977-b17","doi-asserted-by":"crossref","unstructured":"Chaerkady R, Shao H, Scott S-G, Pandey A, Jun AS, Chakravarti S. The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration. J Proteomics. 2013; 87: 122\u2013131.","DOI":"10.1016\/j.jprot.2013.05.023"},{"key":"i1552-5783-59-7-2977-b18","doi-asserted-by":"crossref","unstructured":"Baird TD, Wek RC. Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv Nutr Int Rev J. 2012; 3: 307\u2013321.","DOI":"10.3945\/an.112.002113"},{"key":"i1552-5783-59-7-2977-b19","doi-asserted-by":"crossref","unstructured":"Wortel IMN, van der Meer LT, Kilberg MS, van Leeuwen FN. Surviving stress: modulation of ATF4-mediated stress responses in normal and malignant cells. Trends Endocrinol Metab. 2017; 28: 794\u2013806.","DOI":"10.1016\/j.tem.2017.07.003"},{"key":"i1552-5783-59-7-2977-b20","doi-asserted-by":"crossref","unstructured":"Rajesh K, Krishnamoorthy J, Kazimierczak U, et al. Phosphorylation of the translation initiation factor eIF2a at serine 51 determines the cell fate decisions of Akt in response to oxidative stress. Cell Death Dis. 2015; 6: e1591.","DOI":"10.1038\/cddis.2014.554"},{"key":"i1552-5783-59-7-2977-b21","doi-asserted-by":"crossref","unstructured":"Foster J, Wu WH, Scott SG, et al. Transforming growth factor \u00df and insulin signal changes in stromal fibroblasts of individual keratoconus patients. PLoS One. 2014; 9: e106556.","DOI":"10.1371\/journal.pone.0106556"},{"key":"i1552-5783-59-7-2977-b22","doi-asserted-by":"crossref","unstructured":"Foster JW, Gouveia RM, Connon CJ. Low-glucose enhances keratocyte-characteristic phenotype from corneal stromal cells in serum-free conditions. Sci Rep. 2015; 5: 10839.","DOI":"10.1038\/srep10839"},{"key":"i1552-5783-59-7-2977-b23","doi-asserted-by":"crossref","unstructured":"Scott S-G, Jun AS, Chakravarti S. Sphere formation from corneal keratocytes and phenotype specific markers. Exp Eye Res. 2011; 93: 898\u2013905.","DOI":"10.1016\/j.exer.2011.10.004"},{"key":"i1552-5783-59-7-2977-b24","doi-asserted-by":"crossref","unstructured":"Houghton PE, Keefer KA, Diegelmann RF, Krummel TM. A simple method to assess the relative amount of collagen deposition in wounded fetal mouse limbs. Wound Repair Regen. 1996; 4: 489\u2013495.","DOI":"10.1046\/j.1524-475X.1996.40414.x"},{"key":"i1552-5783-59-7-2977-b25","doi-asserted-by":"crossref","unstructured":"Toth M, Fridman R. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods Mol Med. 2001; 57: 163\u2013174.","DOI":"10.1385\/1-59259-136-1:163"},{"key":"i1552-5783-59-7-2977-b26","doi-asserted-by":"crossref","unstructured":"Pei Y, Sherry DM, McDermott AM. Thy-1 distinguishes human corneal fibroblasts and myofibroblasts from keratocytes. Exp Eye Res. 2004; 79: 705\u2013712.","DOI":"10.1016\/j.exer.2004.08.002"},{"key":"i1552-5783-59-7-2977-b27","doi-asserted-by":"crossref","unstructured":"Foster J, Wu WH, Scott S-G, et al. Transforming growth factor \u00df and insulin signal changes in stromal fibroblasts of individual keratoconus patients. PLoS One. 2014; 9: e106556.","DOI":"10.1371\/journal.pone.0106556"},{"key":"i1552-5783-59-7-2977-b28","doi-asserted-by":"crossref","unstructured":"Estey T, Piatigorsky J, Lassen N, Vasiliou V. ALDH3A1: a corneal crystallin with diverse functions. Exp Eye Res. 2007; 84: 3\u201312.","DOI":"10.1016\/j.exer.2006.04.010"},{"key":"i1552-5783-59-7-2977-b29","doi-asserted-by":"crossref","unstructured":"Ishida Y, Nagata K. Hsp47 as a collagen-specific molecular chaperone. Methods Enzymol. 2011; 499: 167\u2013182.","DOI":"10.1016\/B978-0-12-386471-0.00009-2"},{"key":"i1552-5783-59-7-2977-b30","doi-asserted-by":"crossref","unstructured":"Ma W, Goldberg J. TANGO1\/cTAGE5 receptor as a polyvalent template for assembly of large COPII coats. Proc Natl Acad Sci U S A. 2016; 113: 10061\u201310066.","DOI":"10.1073\/pnas.1605916113"},{"key":"i1552-5783-59-7-2977-b31","doi-asserted-by":"crossref","unstructured":"Michalak M, Corbett EF, Mesaeli N, Nakamura K, Opas M. Calreticulin: one protein, one gene, many functions. Biochem J. 1999; 344: 281\u2013292.","DOI":"10.1042\/bj3440281"},{"key":"i1552-5783-59-7-2977-b32","doi-asserted-by":"crossref","unstructured":"Scott IC, Blitz IL, Pappano WN, et al. Mammalian BMP-1\/tolloid-related metalloproteinases, including novel family member mammalian tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis. Dev Biol. 1999; 213: 283\u2013300.","DOI":"10.1006\/dbio.1999.9383"},{"key":"i1552-5783-59-7-2977-b33","doi-asserted-by":"crossref","unstructured":"Bourhis J-M, Vadon-Le Goff S, Afrache H, et al. Procollagen C-proteinase enhancer grasps the stalk of the C-propeptide trimer to boost collagen precursor maturation. Proc Natl Acad Sci U S A. 2013; 110: 6394\u20136399.","DOI":"10.1073\/pnas.1300480110"},{"key":"i1552-5783-59-7-2977-b34","doi-asserted-by":"crossref","unstructured":"Li SW, Arita M, Fertala A, et al. Transgenic mice with inactive alleles for procollagen N-proteinase (ADAMTS-2) develop fragile skin and male sterility. Biochem J. 2001; 355: 271\u2013278.","DOI":"10.1042\/bj3550271"},{"key":"i1552-5783-59-7-2977-b35","doi-asserted-by":"crossref","unstructured":"Harding HP, Zhang Y, Zeng H, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell. 2003; 11: 619\u2013633.","DOI":"10.1016\/S1097-2765(03)00105-9"},{"key":"i1552-5783-59-7-2977-b36","doi-asserted-by":"crossref","unstructured":"B'chir W, Maurin A-C, Carraro V, et al. The eIF2a\/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 2013; 41: 7683\u2013799.","DOI":"10.1093\/nar\/gkt563"},{"key":"i1552-5783-59-7-2977-b37","doi-asserted-by":"crossref","unstructured":"Segev F, H\u00e9on E, Cole WG, et al. Structural abnormalities of the cornea and lid resulting from collagen V mutations. Invest Ophthalmol Vis Sci. 2006; 47: 565\u2013573.","DOI":"10.1167\/iovs.05-0771"},{"key":"i1552-5783-59-7-2977-b38","doi-asserted-by":"crossref","unstructured":"Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H. Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol. 1998; 141: 1277\u20131286.","DOI":"10.1083\/jcb.141.5.1277"},{"key":"i1552-5783-59-7-2977-b39","doi-asserted-by":"crossref","unstructured":"Shao H, Chaerkady R, Chen S, et al. Proteome profiling of wild type and lumican-deficient mouse corneas. J Proteomics. 2011; 74: 1895\u20131905.","DOI":"10.1016\/j.jprot.2011.04.032"},{"key":"i1552-5783-59-7-2977-b40","doi-asserted-by":"crossref","unstructured":"Liu CY, Birk DE, Hassell JR, Kane B, Kao WWY. Keratocan-deficient mice display alterations in corneal structure. J Biol Chem. 2003; 278: 21672\u201321677.","DOI":"10.1074\/jbc.M301169200"},{"key":"i1552-5783-59-7-2977-b41","doi-asserted-by":"crossref","unstructured":"Nagata K. Expression and function of heat shock protein 47: a collagen-specific molecular chaperone in the endoplasmic reticulum. Matrix Biol. 1998; 16: 379\u2013386.","DOI":"10.1016\/S0945-053X(98)90011-7"},{"key":"i1552-5783-59-7-2977-b42","doi-asserted-by":"crossref","unstructured":"Nagata K. HSP47 as a collagen-specific molecular chaperone: function and expression in normal mouse development. Semin Cell Dev Biol. 2003; 14: 275\u2013282.","DOI":"10.1016\/j.semcdb.2003.09.020"},{"key":"i1552-5783-59-7-2977-b43","doi-asserted-by":"crossref","unstructured":"Vadon-Le Goff S, Hulmes DJS, Moali C . BMP-1\/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling. Matrix Biol. 2015; 44\u201346: 14\u201323.","DOI":"10.1016\/j.matbio.2015.02.006"},{"key":"i1552-5783-59-7-2977-b44","doi-asserted-by":"crossref","unstructured":"Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002; 50: 341\u2013351.","DOI":"10.1177\/002215540205000306"},{"key":"i1552-5783-59-7-2977-b45","doi-asserted-by":"crossref","unstructured":"Cristina Kenney M, Brown DJ . The cascade hypothesis of keratoconus. Contact Lens Anterior Eye. 2003; 26: 139\u2013146.","DOI":"10.1016\/S1367-0484(03)00022-5"},{"key":"i1552-5783-59-7-2977-b46","doi-asserted-by":"crossref","unstructured":"McPherson SD, Kiffney GT. Some histologic findings in keratoconus. Arch Ophthalmol. 1968; 79: 669\u2013673.","DOI":"10.1001\/archopht.1968.03850040671004"},{"key":"i1552-5783-59-7-2977-b47","doi-asserted-by":"crossref","unstructured":"Jun AS, Cope L, Speck C, et al. Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS One. 2011; 6: e16437.","DOI":"10.1371\/journal.pone.0016437"},{"key":"i1552-5783-59-7-2977-b48","doi-asserted-by":"crossref","unstructured":"Acera A, Vecino E, Rodr\u00edguez-Agirretxe I, et al. Changes in tear protein profile in keratoconus disease. Eye (Lond). 2011; 25: 1225\u20131233.","DOI":"10.1038\/eye.2011.105"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?articleid=2684837","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:30:54Z","timestamp":1791927054000},"score":1,"resource":{"primary":{"URL":"http:\/\/iovs.arvojournals.org\/article.aspx?doi=10.1167\/iovs.18-24367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,11]]},"references-count":48,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,6,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.18-24367","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2018,6,11]]}}}