{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:21:39Z","timestamp":1790752899761,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":688,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Alonzo Family Fund"},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Modeling age-related macular degeneration (AMD) is challenging, because it is a multifactorial disease. To focus on interactions between the retinal pigment epithelium (RPE) and Bruch's membrane, we generated RPE from AMD patients and used an altered extracellular matrix (ECM) that models aged Bruch's membrane. Induced pluripotent stem cells (iPSCs) were generated from fibroblasts isolated from AMD patients or age-matched (normal) controls. RPE derived from iPSCs were analyzed by morphology, marker expression, transepithelial electrical resistance (TER), and phagocytosis of rod photoreceptor outer segments. Cell attachment and viability was tested on nitrite-modified ECM, a typical modification of aged Bruch's membrane. DNA microarrays with hierarchical clustering and analysis of mitochondrial function were used to elucidate possible mechanisms for the observed phenotypes. Differentiated RPE displayed cell-specific morphology and markers. The TER and phagocytic capacity were similar among iPSC-derived RPE cultures. However, distinct clusters were found for the transcriptomes of AMD and control iPSC-derived RPE. AMD-derived iPSC-RPE downregulated genes responsible for metabolic-related pathways and cell attachment. AMD-derived iPSC-RPE exhibited reduced mitochondrial respiration and ability to attach and survive on nitrite-modified ECM. Cells that did attach induced the expression of complement genes. Despite reprogramming, iPSC derived from AMD patients yielded RPE with a transcriptome that is distinct from that of age-matched controls. When challenged with an AMD-like modification of Bruch's membrane, AMD-derived iPSC-RPE activated the complement immune system.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance statement Age-related macular degeneration (AMD) is a multifactorial disease of primates, which confounds efforts to model the disease in laboratory animals or in culture. The present culture model mimics aspects of the disease, as demonstrated by using stem cells derived from patients. The disease involves interactions between the retinal pigment epithelium, a layer of cells necessary for the function of photoreceptors, and the extracellular matrix upon which the epithelium sits. The differences observed between epithelia derived from normal and AMD patients were exacerbated when cells were cultured on a mimetic for diseased matrix. This model provides a robust platform for developing therapeutics.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.19-0321","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T10:31:14Z","timestamp":1576492274000},"page":"364-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions"],"prefix":"10.1093","volume":"9","author":[{"given":"Jie","family":"Gong","sequence":"first","affiliation":[{"name":"1 Department of Ophthalmology and Visual Science Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"1 Department of Ophthalmology and Visual Science Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NYSCF Global Stem Cell Array Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Noggle","sequence":"additional","affiliation":[{"name":"2 The New York Stem Cell Foundation (NYSCF) Research Institute, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Paull","sequence":"additional","affiliation":[{"name":"2 The New York Stem Cell Foundation (NYSCF) Research Institute, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Rizzolo","sequence":"additional","affiliation":[{"name":"1 Department of Ophthalmology and Visual Science Yale University School of Medicine, New Haven, Connecticut"},{"name":"3 Department of Surgery Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian V.","family":"Del Priore","sequence":"additional","affiliation":[{"name":"1 Department of Ophthalmology and Visual Science Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Fields","sequence":"additional","affiliation":[{"name":"1 Department of Ophthalmology and Visual Science Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"2022022809285677900_sct312648-bib-0001","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1136\/bjo.76.10.607","article-title":"Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula","volume":"76","author":"Marshall","year":"1992","journal-title":"Br J Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0002","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0161-6420(90)32619-2","article-title":"Aging changes in Bruch's membrane. A histochemical and morphologic study","volume":"97","author":"Pauleikhoff","year":"1990","journal-title":"Ophthalmology"},{"key":"2022022809285677900_sct312648-bib-0003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2009.08.003","article-title":"The dynamic nature of Bruch's membrane","volume":"29","author":"Booij","year":"2010","journal-title":"Prog Retin Eye Res"},{"key":"2022022809285677900_sct312648-bib-0004","first-page":"1271","article-title":"Phagocytosis and H2O2 induce catalase and metallothionein gene expression in human retinal pigment epithelial cells","volume":"36","author":"Tate","year":"1995","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809285677900_sct312648-bib-0005","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0039-6257(98)00002-2","article-title":"The association between cigarette smoking and ocular diseases","volume":"42","author":"Solberg","year":"1998","journal-title":"Surv Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0006","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/ije\/16.1.31","article-title":"Nitric oxide yields of contemporary UK, US and French cigarettes","volume":"16","author":"Borland","year":"1987","journal-title":"Int J Epidemiol"},{"key":"2022022809285677900_sct312648-bib-0007","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0008","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.exer.2010.01.014","article-title":"Age-related accumulation of 3-nitrotyrosine and nitro-A2E in human Bruch's membrane","volume":"90","author":"Murdaugh","year":"2010","journal-title":"Exp Eye Res"},{"key":"2022022809285677900_sct312648-bib-0009","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.niox.2018.07.006","article-title":"Nitrite ion modifies tyrosine and lysine residues of extracellular matrix proteins","volume":"79","author":"Thao","year":"2018","journal-title":"Nitric Oxide"},{"key":"2022022809285677900_sct312648-bib-0010","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/emm.2007.9","article-title":"Tyrosine nitration site specificity identified by LC\/MS in nitrite-modified collagen type IV","volume":"39","author":"Wang","year":"2007","journal-title":"Exp Mol Med"},{"key":"2022022809285677900_sct312648-bib-0011","doi-asserted-by":"crossref","first-page":"14534","DOI":"10.1074\/jbc.M114.564674","article-title":"Smoke-exposure causes endoplasmic reticulum stress and lipid accumulation in retinal pigment epithelium through oxidative stress and complement activation","volume":"289","author":"Kunchithapautham","year":"2014","journal-title":"J Biol Chem"},{"key":"2022022809285677900_sct312648-bib-0012","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2741\/S380","article-title":"Potential of epigenetic mechanisms in AMD pathology","volume":"5","author":"Blasiak","year":"2013","journal-title":"Front Biosci (Schol Ed)"},{"key":"2022022809285677900_sct312648-bib-0013","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/APO.0b013e31829e2793","article-title":"Genetic and epigenetic regulation in age-related macular degeneration","volume":"2","author":"Wei","year":"2013","journal-title":"Asia Pac J Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0014","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13148-019-0608-2","article-title":"Whole-genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration reveals differential methylation of the SKI, GTF2H4, and TNXB genes","volume":"11","author":"Porter","year":"2019","journal-title":"Clin Epigenetics"},{"key":"2022022809285677900_sct312648-bib-0015","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1080\/15592294.2015.1060388","article-title":"Differential DNA methylation identified in the blood and retina of AMD patients","volume":"10","author":"Oliver","year":"2015","journal-title":"Epigenetics"},{"key":"2022022809285677900_sct312648-bib-0016","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2019.107701","article-title":"Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells","volume":"189","author":"Nashine","year":"2019","journal-title":"Exp Eye Res"},{"issue":"Suppl 1","key":"2022022809285677900_sct312648-bib-0017","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/S0039-6257(99)00086-7","article-title":"Histologic and morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes","volume":"44","author":"Spraul","year":"1999","journal-title":"Surv Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0047-6374(98)00119-5","article-title":"Mechanisms of maturation and ageing of collagen","volume":"106","author":"Bailey","year":"1998","journal-title":"Mech Ageing Dev"},{"key":"2022022809285677900_sct312648-bib-0019","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/03008200109014253","article-title":"The nitrite\/collagen reaction: non-enzymatic nitration as a model system for age-related damage","volume":"42","author":"Paik","year":"2001","journal-title":"Connect Tissue Res"},{"key":"2022022809285677900_sct312648-bib-0020","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1136\/bjo.87.2.212","article-title":"Distribution of the collagen IV isoforms in human Bruch's membrane","volume":"87","author":"Chen","year":"2003","journal-title":"Br J Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0021","first-page":"1110","article-title":"Reattachment of cultured human retinal pigment epithelium to extracellular matrix and human Bruch's membrane","volume":"38","author":"Ho","year":"1997","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809285677900_sct312648-bib-0022","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF01007836","article-title":"Reattachment to a substrate prevents apoptosis of human retinal pigment epithelium","volume":"235","author":"Tezel","year":"1997","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0023","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1001\/archopht.116.3.335","article-title":"Reattachment rate of human retinal pigment epithelium to layers of human Bruch's membrane","volume":"116","author":"Del Priore","year":"1998","journal-title":"Arch Ophthalmol"},{"key":"2022022809285677900_sct312648-bib-0024","first-page":"499","article-title":"Analysis of retinal pigment epithelium integrin expression and adhesion to aged submacular human Bruch's membrane","volume":"101","author":"Zarbin","year":"2003","journal-title":"Trans Am Ophthalmol Soc"},{"key":"2022022809285677900_sct312648-bib-0025","first-page":"123","article-title":"Retinal pigment epithelium resurfacing of aged submacular human Bruch's membrane","volume":"102","author":"Gullapalli","year":"2004","journal-title":"Trans Am Ophthalmol Soc"},{"key":"2022022809285677900_sct312648-bib-0026","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1080\/02713680590968259","article-title":"Nitrite-modified extracellular matrix proteins deleteriously affect retinal pigment epithelial cell function and viability: a comparison study with nonenzymatic glycation mechanisms","volume":"30","author":"Wang","year":"2005","journal-title":"Curr Eye Res"},{"key":"2022022809285677900_sct312648-bib-0027","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3390\/jcm4040567","article-title":"Patient-specific iPSC-derived RPE for modeling of retinal diseases","volume":"4","author":"Nguyen","year":"2015","journal-title":"J Clin Med"},{"key":"2022022809285677900_sct312648-bib-0028","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/0300985809359598","article-title":"Animals as models of age-related macular degeneration: an imperfect measure of the truth","volume":"47","author":"Zeiss","year":"2010","journal-title":"Vet Pathol"},{"key":"2022022809285677900_sct312648-bib-0029","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 USA"},{"key":"2022022809285677900_sct312648-bib-0030","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 USA"},{"key":"2022022809285677900_sct312648-bib-0031","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":"2022022809285677900_sct312648-bib-0032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0177763","article-title":"Extracellular matrix nitration alters growth factor release and activates bioactive complement in human retinal pigment epithelial cells","volume":"12","author":"Fields","year":"2017","journal-title":"PLoS One"},{"key":"2022022809285677900_sct312648-bib-0033","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1167\/iovs.15-16438","article-title":"Nitrite modification of extracellular matrix alters CD46 expression and VEGF release in human retinal pigment epithelium","volume":"56","author":"Fields","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809285677900_sct312648-bib-0034","article-title":"Culturing of retinal pigment epithelial cells on an ex vivo model of aged human Bruch's membrane","volume":"134","author":"Cai","year":"2018","journal-title":"JoVE"},{"key":"2022022809285677900_sct312648-bib-0035","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.4.5.10","article-title":"Reengineering human Bruch's membrane increases rod outer segment phagocytosis by human retinal pigment epithelium","volume":"4","author":"Moreira","year":"2015","journal-title":"Transl Vis Sci Technol"},{"key":"2022022809285677900_sct312648-bib-0036","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12967-016-1101-8","article-title":"Repressed SIRT1\/PGC-1alpha pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration","volume":"14","author":"Golestaneh","year":"2016","journal-title":"J Transl Med"},{"key":"2022022809285677900_sct312648-bib-0037","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.stem.2016.12.015","article-title":"Nicotinamide ameliorates disease phenotypes in a human iPSC model of age-related macular degeneration","volume":"20","author":"Saini","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2022022809285677900_sct312648-bib-0038","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nmeth.3507","article-title":"Automated, high-throughput derivation, characterization and differentiation of induced pluripotent stem cells","volume":"12","author":"Paull","year":"2015","journal-title":"Nat Methods"},{"key":"2022022809285677900_sct312648-bib-0039","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0143272","article-title":"Differentiation of human protein-induced pluripotent stem cells toward a retinal pigment epithelial cell fate","volume":"10","author":"Gong","year":"2015","journal-title":"PLoS One"},{"key":"2022022809285677900_sct312648-bib-0040","doi-asserted-by":"crossref","first-page":"217","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":"2022022809285677900_sct312648-bib-0041","doi-asserted-by":"crossref","first-page":"6767","DOI":"10.1167\/iovs.13-11943","article-title":"Functional analysis of serially expanded human iPS cell-derived RPE cultures","volume":"54","author":"Singh","year":"2013","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809285677900_sct312648-bib-0042","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1167\/iovs.11-8311","article-title":"Effects of proinflammatory cytokines on the claudin-19 rich tight junctions of human retinal pigment epithelium","volume":"53","author":"Peng","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022022809285677900_sct312648-bib-0043","doi-asserted-by":"crossref","first-page":"534","DOI":"10.5966\/sctm.2012-0134","article-title":"Engineering a blood-retinal barrier with human embryonic stem cell-derived retinal pigment epithelium: transcriptome and functional analysis","volume":"2","author":"Peng","year":"2013","journal-title":"Stem Cells Translational Medicine"},{"key":"2022022809285677900_sct312648-bib-0044","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1101\/gr.10.4.431","article-title":"Systematic management and analysis of yeast gene expression data","volume":"10","author":"Aach","year":"2000","journal-title":"Genome Res"},{"key":"2022022809285677900_sct312648-bib-0045","doi-asserted-by":"crossref","first-page":"D661","DOI":"10.1093\/nar\/gkx1064","article-title":"WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research","volume":"46","author":"Slenter","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2022022809285677900_sct312648-bib-0046","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol"},{"key":"2022022809285677900_sct312648-bib-0047","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-1-4939-3335-8_17","article-title":"Analysis of TLR-induced metabolic changes in dendritic cells using the seahorse XF(e)96 extracellular flux Analyzer","volume":"1390","author":"Pelgrom","year":"2016","journal-title":"Methods Mol Biol"},{"key":"2022022809285677900_sct312648-bib-0048","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-319-75402-4_4","article-title":"Alterations in extracellular matrix\/Bruch's membrane can cause the activation of the alternative complement pathway via tick-over","volume":"1074","author":"Fernandez-Godino","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2022022809285677900_sct312648-bib-0049","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/hmg\/ddx392","article-title":"Changes in extracellular matrix cause RPE cells to make basal deposits and activate the alternative complement pathway","volume":"27","author":"Fernandez-Godino","year":"2018","journal-title":"Hum Mol Genet"},{"key":"2022022809285677900_sct312648-bib-0050","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/acs.jmedchem.5b00789","article-title":"Patient-specific induced pluripotent stem cells for disease modeling and phenotypic drug discovery","volume":"59","author":"Tang","year":"2016","journal-title":"J Med Chem"},{"key":"2022022809285677900_sct312648-bib-0051","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.brainres.2015.12.011","article-title":"Looking into the future: using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling","volume":"1638","author":"Song","year":"2016","journal-title":"Brain Res"},{"key":"2022022809285677900_sct312648-bib-0052","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bbagen.2015.05.016","article-title":"Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration","volume":"1860","author":"Kannan","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"2022022809285677900_sct312648-bib-0053","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.exer.2004.12.011","article-title":"Crystallin distribution in Bruch's membrane-choroid complex from AMD and age-matched donor eyes","volume":"80","author":"Nakata","year":"2005","journal-title":"Exp Eye Res"},{"key":"2022022809285677900_sct312648-bib-0054","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1182\/blood-2009-01-197095","article-title":"alphaB-crystallin regulation of angiogenesis by modulation of VEGF","volume":"115","author":"Kase","year":"2010","journal-title":"Blood"},{"key":"2022022809285677900_sct312648-bib-0055","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/gm315","article-title":"Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks","volume":"4","author":"Newman","year":"2012","journal-title":"Genome Med"},{"key":"2022022809285677900_sct312648-bib-0056","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0955-0674(03)00096-6","article-title":"Interactions between growth factor receptors and adhesion molecules: breaking the rules","volume":"15","author":"Comoglio","year":"2003","journal-title":"Curr Opin Cell Biol"},{"key":"2022022809285677900_sct312648-bib-0057","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1242\/jcs.00373","article-title":"Focal adhesion kinase: the first ten years","volume":"116","author":"Parsons","year":"2003","journal-title":"J Cell Sci"},{"key":"2022022809285677900_sct312648-bib-0058","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0248-4900(00)01101-1","article-title":"Focal adhesions: structure and dynamics","volume":"92","author":"Petit","year":"2000","journal-title":"Biol Cell"},{"key":"2022022809285677900_sct312648-bib-0059","doi-asserted-by":"crossref","first-page":"346","DOI":"10.18632\/aging.100303","article-title":"mTOR pathway activation in age-related retinal disease","volume":"3","author":"Zhao","year":"2011","journal-title":"Aging"},{"key":"2022022809285677900_sct312648-bib-0060","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1076\/ceyr.25.2.79.10158","article-title":"Extracellular matrix ligands promote RPE attachment to inner Bruch's membrane","volume":"25","author":"Del Priore","year":"2002","journal-title":"Curr Eye Res"},{"issue":"8","key":"2022022809285677900_sct312648-bib-0061","first-page":"1","article-title":"Effects of aging and anatomic location on gene expression in human retina","volume":"4","author":"Cai","year":"2012","journal-title":"Frontiers Aging Neurosci"},{"key":"2022022809285677900_sct312648-bib-0062","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms15374","article-title":"Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors","volume":"8","author":"Benedicto","year":"2017","journal-title":"Nat Commun"},{"key":"2022022809285677900_sct312648-bib-0063","doi-asserted-by":"crossref","first-page":"C744","DOI":"10.1152\/ajpcell.2000.279.3.C744","article-title":"Differential regulation of tight junction permeability during development of the retinal pigment epithelium","volume":"279","author":"Ban","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"key":"2022022809285677900_sct312648-bib-0064","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1089\/jop.2015.0157","article-title":"Nanofiber scaffold-based tissue-engineered retinal pigment epithelium to treat degenerative eye diseases","volume":"32","author":"Hotaling","year":"2016","journal-title":"J Ocul Pharmacol Ther"},{"key":"2022022809285677900_sct312648-bib-0065","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat Immunol"},{"key":"2022022809285677900_sct312648-bib-0066","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","article-title":"Clinical classification of age-related macular degeneration","volume":"120","author":"Ferris","year":"2013","journal-title":"Ophthalmology"},{"key":"2022022809285677900_sct312648-bib-0067","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsctm.19-0321","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/sctm.19-0321","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/sctm.19-0321","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/364\/42627957\/stcltm_9_3_364.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/9\/3\/364\/42627957\/stcltm_9_3_364.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:31:37Z","timestamp":1646040697000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/9\/3\/364\/6407148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,16]]},"references-count":67,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,12,16]]},"published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.19-0321","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2019,12,16]]},"assertion":[{"value":"2019-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}