{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:46:37Z","timestamp":1792651597337,"version":"4.5.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1016\/j.exer.2021.108899","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T02:02:53Z","timestamp":1639706573000},"page":"108899","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"special_numbering":"C","title":["Extracellular matrix dysfunction in Sorsby patient-derived retinal pigment epithelium"],"prefix":"10.1016","volume":"215","author":[{"given":"Abbi L.","family":"Engel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YeKai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Khuu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Worrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Manson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayne R.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlen","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Yanagida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Hua","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind","family":"Ramakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Weleber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Anand-Apte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Hurley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhai","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6859-5552","authenticated-orcid":false,"given":"Jennifer R.","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2021.108899_bib1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jnr.24317","article-title":"Sorsby fundus dystrophy: insights from the past and looking to the future","volume":"97","author":"Anand-Apte","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.exer.2021.108899_bib2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The role of TIMPs in regulation of extracellular matrix proteolysis","volume":"44\u201346","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"10.1016\/j.exer.2021.108899_bib3","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1006\/exer.2001.1089","article-title":"Measurement of TIMP-3 expression and Bruch's membrane thickness in human macula","volume":"73","author":"Bailey","year":"2001","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2021.108899_bib4","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.exer.2021.108899_bib5","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.omtm.2019.10.014","article-title":"AAV-mediated gene augmentation therapy restores critical functions in mutant PRPF31(+\/-) iPSC-derived RPE cells","volume":"15","author":"Brydon","year":"2019","journal-title":"Mol Ther-Meth Clin D"},{"key":"10.1016\/j.exer.2021.108899_bib6","doi-asserted-by":"crossref","first-page":"384","DOI":"10.5966\/sctm.2012-0163","article-title":"Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium","volume":"2","author":"Buchholz","year":"2013","journal-title":"Stem Cells Transl Med"},{"key":"10.1016\/j.exer.2021.108899_bib7","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1001\/archopht.1996.01100130729016","article-title":"Sorsby fundus dystrophy. A family with the Ser181Cys mutation of the tissue inhibitor of metalloproteinases 3","volume":"114","author":"Carrero-Valenzuela","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.exer.2021.108899_bib8","first-page":"898","article-title":"TIMP-3, collagen, and elastin immunohistochemistry and histopathology of Sorsby's fundus dystrophy","volume":"41","author":"Chong","year":"2000","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib9","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/S0002-9394(03)00482-3","article-title":"TIMP-3 mRNA is not overexpressed in Sorsby fundus dystrophy","volume":"136","author":"Chong","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2021.108899_bib10","first-page":"23","article-title":"Pathophysiology of non-neovascular age-related macular degeneration: the oil spill in Bruch's membrane and beyond","volume":"228","author":"Curcio","year":"2012","journal-title":"Ophthalmologica"},{"key":"10.1016\/j.exer.2021.108899_bib11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/29.5.7252127","article-title":"An electron microscopic histochemical and analytical X-ray microprobe study of calcification in Bruch's membrane from human eyes","volume":"29","author":"Davis","year":"1981","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.exer.2021.108899_bib12","doi-asserted-by":"crossref","first-page":"14710","DOI":"10.1073\/pnas.1604572113","article-title":"Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium","volume":"113","author":"Du","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2021.108899_bib13","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1136\/bjo.82.11.1329","article-title":"Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby's fundus dystrophy or retinitis pigmentosa","volume":"82","author":"Fariss","year":"1998","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.exer.2021.108899_bib14","doi-asserted-by":"crossref","first-page":"E8214","DOI":"10.1073\/pnas.1710430114","article-title":"Drusen in patient-derived hiPSC-RPE models of macular dystrophies","volume":"114","author":"Galloway","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2021.108899_bib15","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.ophtha.2015.04.035","article-title":"Reticular pseudodrusen in Sorsby fundus dystrophy","volume":"122","author":"Gliem","year":"2015","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2021.108899_bib16","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/sctm.19-0321","article-title":"Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions","volume":"9","author":"Gong","year":"2020","journal-title":"Stem Cells Transl Med"},{"key":"10.1016\/j.exer.2021.108899_bib17","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00441-009-0844-4","article-title":"Collagens","volume":"339","author":"Gordon","year":"2010","journal-title":"Cell Tissue Res."},{"key":"10.1016\/j.exer.2021.108899_bib18","doi-asserted-by":"crossref","DOI":"10.1186\/s13287-017-0652-9","article-title":"Differentiation of RPE cells from integration-free iPS cells and their cell biological characterization","volume":"8","author":"Hazim","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.exer.2021.108899_bib19","series-title":"Histology of the Human Eye : an Atlas and Textbook","author":"Hogan","year":"1971"},{"key":"10.1016\/j.exer.2021.108899_bib20","doi-asserted-by":"crossref","DOI":"10.1002\/path.5506","article-title":"In vitro stem cell modelling demonstrates a proof-of-concept for excess functional mutant TIMP3 as the cause of Sorsby Fundus Dystrophy","author":"Hongisto","year":"2020","journal-title":"J. Pathol."},{"key":"10.1016\/j.exer.2021.108899_bib21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/nrc.2016.115","article-title":"TIMPs: versatile extracellular regulators in cancer","volume":"17","author":"Jackson","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.exer.2021.108899_bib22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng0995-27","article-title":"Night blindness in Sorsby's fundus dystrophy reversed by vitamin A","volume":"11","author":"Jacobson","year":"1995","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2021.108899_bib23","first-page":"2782","article-title":"Regulation of RPE intercellular junction integrity and function by hepatocyte growth factor","volume":"43","author":"Jin","year":"2002","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib24","doi-asserted-by":"crossref","first-page":"18277","DOI":"10.1073\/pnas.1109703108","article-title":"Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration","volume":"108","author":"Johnson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2021.108899_bib25","first-page":"2367","article-title":"TIMP-3 in Bruch's membrane: changes during aging and in age-related macular degeneration","volume":"40","author":"Kamei","year":"1999","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.preteyeres.2016.04.008","article-title":"Differentiating drusen: drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes","volume":"53","author":"Khan","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2021.108899_bib27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1006\/jsbi.2002.4449","article-title":"Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy","volume":"137","author":"Knupp","year":"2002","journal-title":"J. Struct. Biol."},{"key":"10.1016\/j.exer.2021.108899_bib28","first-page":"1772","article-title":"Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration","volume":"37","author":"Kuntz","year":"1996","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib29","doi-asserted-by":"crossref","first-page":"101514","DOI":"10.1016\/j.scr.2019.101514","article-title":"Robust induction of retinal pigment epithelium cells from human induced pluripotent stem cells by inhibiting FGF\/MAPK signaling","volume":"39","author":"Kuroda","year":"2019","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.exer.2021.108899_bib30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00726-017-2490-6","article-title":"Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth","volume":"50","author":"Li","year":"2018","journal-title":"Amino Acids"},{"key":"10.1016\/j.exer.2021.108899_bib31","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1167\/iovs.16-21060","article-title":"Subretinal pigment epithelial deposition of drusen components including hydroxyapatite in a primary cell culture model","volume":"58","author":"Pilgrim","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib32","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10495-014-1076-y","article-title":"Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism","volume":"20","author":"Qi","year":"2015","journal-title":"Apoptosis"},{"key":"10.1016\/j.exer.2021.108899_bib33","doi-asserted-by":"crossref","first-page":"19927","DOI":"10.1074\/jbc.M109.013763","article-title":"S156C mutation in tissue inhibitor of metalloproteinases-3 induces increased angiogenesis","volume":"284","author":"Qi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.exer.2021.108899_bib34","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1167\/iovs.06-0443","article-title":"Relationship of Basal laminar deposit and membranous debris to the clinical presentation of early age-related macular degeneration","volume":"48","author":"Sarks","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib35","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1146\/annurev.biochem.77.032207.120833","article-title":"Collagen structure and stability","volume":"78","author":"Shoulders","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.exer.2021.108899_bib36","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nprot.2009.33","article-title":"A protocol for the culture and differentiation of highly polarized human retinal pigment epithelial cells","volume":"4","author":"Sonoda","year":"2009","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.exer.2021.108899_bib37","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-1-4614-0631-0_34","article-title":"A review and update on the molecular basis of pathogenesis of Sorsby fundus dystrophy","volume":"723","author":"Stohr","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.exer.2021.108899_bib38","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/IAE.0000000000000503","article-title":"Refractile drusen: clinical imaging and candidate histology","volume":"35","author":"Suzuki","year":"2015","journal-title":"Retina"},{"key":"10.1016\/j.exer.2021.108899_bib39","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aat4544","article-title":"Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration","volume":"10","author":"Tan","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.exer.2021.108899_bib40","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1073\/pnas.1413347112","article-title":"Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye","volume":"112","author":"Thompson","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2021.108899_bib41","article-title":"Abundant lipid and protein components of drusen","volume":"5","author":"Wang","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2021.108899_bib42","first-page":"2732","article-title":"A mouse model for Sorsby fundus dystrophy","volume":"43","author":"Weber","year":"2002","journal-title":"Invest. Ophth. Vis. Sci."},{"key":"10.1016\/j.exer.2021.108899_bib43","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/ng1294-352","article-title":"Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy","volume":"8","author":"Weber","year":"1994","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2021.108899_bib44","doi-asserted-by":"crossref","first-page":"101681","DOI":"10.1016\/j.redox.2020.101681","article-title":"The retinal pigment epithelium in Sorsby Fundus Dystrophy shows increased sensitivity to oxidative stress-induced degeneration","volume":"37","author":"Wolk","year":"2020","journal-title":"Redox Biol."},{"key":"10.1016\/j.exer.2021.108899_bib45","first-page":"70","article-title":"Comparison of histologic findings in age-related macular degeneration with RPE flatmount images","volume":"25","author":"Zhang","year":"2019","journal-title":"Mol. Vis."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483521004656?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483521004656?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:17:11Z","timestamp":1757999831000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483521004656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":45,"alternative-id":["S0014483521004656"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2021.108899","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.06.425613","asserted-by":"object"}]},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Extracellular matrix dysfunction in Sorsby patient-derived retinal pigment epithelium","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2021.108899","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108899"}}