{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:34Z","timestamp":1792789534767,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PT13\/0001\/0041"],"award-info":[{"award-number":["PT13\/0001\/0041"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3 Carmen i M\u00aa Jos\u00e9 God\u00f3","award":["Fundaci\u00f3 CMJ God\u00f3 2017"],"award-info":[{"award-number":["Fundaci\u00f3 CMJ God\u00f3 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.<\/jats:p>","DOI":"10.3390\/ijms221910497","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:38:09Z","timestamp":1632865089000},"page":"10497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-5478","authenticated-orcid":false,"given":"Anna","family":"Duarri","sequence":"first","affiliation":[{"name":"Program for Clinical Translation of Regenerative Medicine in Catalonia\u2013P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"National Stem Cell Bank-Barcelona Node, Biomolecular and Bioinformatics Resources Platform PRB2, ISCIII, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Ophthalmology Research Group, Vall d\u2019Hebron Institut de Recerca (VHIR), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3019-8911","authenticated-orcid":false,"given":"Eduardo","family":"Rodr\u00edguez-Bocanegra","sequence":"additional","affiliation":[{"name":"Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain"},{"name":"Institut de la M\u00e0cula, Centro M\u00e9dico Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Mart\u00ednez-Navarrete","sequence":"additional","affiliation":[{"name":"Networking Research Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Institute of Bioengineering, Universidad Miguel Hern\u00e1ndez, 03202 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Biarn\u00e9s","sequence":"additional","affiliation":[{"name":"Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain"},{"name":"Institut de la M\u00e0cula, Centro M\u00e9dico Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain"},{"name":"Institut de la M\u00e0cula, Centro M\u00e9dico Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3741-1220","authenticated-orcid":false,"given":"Luc\u00eda Lee","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain"},{"name":"Institut de la M\u00e0cula, Centro M\u00e9dico Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Program for Clinical Translation of Regenerative Medicine in Catalonia\u2013P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-7755","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Aran","sequence":"additional","affiliation":[{"name":"Program for Clinical Translation of Regenerative Medicine in Catalonia\u2013P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"National Stem Cell Bank-Barcelona Node, Biomolecular and Bioinformatics Resources Platform PRB2, ISCIII, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Specific Pig S.L, 08820 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Aguilera-Xiol","sequence":"additional","affiliation":[{"name":"Specific Pig S.L, 08820 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1812-9323","authenticated-orcid":false,"given":"Ricardo P.","family":"Casaroli-Marano","sequence":"additional","affiliation":[{"name":"Banc de Sang i Teixits (BST), Institute of Biomedical Research (IIB-Sant Pau), 08025 Barcelona, Spain"},{"name":"Department of Surgery, School of Medicine and Health Science, Hospital Clinic de Barcelona, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteve","family":"Trias","sequence":"additional","affiliation":[{"name":"LEITAT Technological Center, 08005 Barcelona, Spain"},{"name":"Advanced Therapies Unit, Hospital Cl\u00ednic de Barcelona, 08005 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-6011","authenticated-orcid":false,"given":"Eduardo","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Networking Research Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Institute of Bioengineering, Universidad Miguel Hern\u00e1ndez, 03202 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2189-9775","authenticated-orcid":false,"given":"\u00c1ngel","family":"Raya","sequence":"additional","affiliation":[{"name":"Program for Clinical Translation of Regenerative Medicine in Catalonia\u2013P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Networking Research Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), 08010 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-9904","authenticated-orcid":false,"given":"Anna","family":"Veiga","sequence":"additional","affiliation":[{"name":"Program for Clinical Translation of Regenerative Medicine in Catalonia\u2013P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"National Stem Cell Bank-Barcelona Node, Biomolecular and Bioinformatics Resources Platform PRB2, ISCIII, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Mon\u00e9s","sequence":"additional","affiliation":[{"name":"Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain"},{"name":"Institut de la M\u00e0cula, Centro M\u00e9dico Teknon, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ophtha.2017.05.035","article-title":"Prevalence of Age-Related Macular De-generation in Europe: The Past and the Future","volume":"124","author":"Colijn","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/eye.2016.216","article-title":"Structural and molecular changes in the aging choroid: Implications for age-related macular degeneration","volume":"31","author":"Chirco","year":"2016","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1124\/mi.10.5.4","article-title":"Age-related Macular Degeneration: Genetic and Environmental Factors of Disease","volume":"10","author":"Chen","year":"2010","journal-title":"Mol. Interv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1080\/14712598.2017.1346079","article-title":"Induced pluripotent stem cell-based therapy for age-related macular degeneration","volume":"17","author":"Bracha","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/ans.13616","article-title":"Advances in implantable bionic devices for blindness: A review","volume":"86","author":"Lewis","year":"2016","journal-title":"ANZ J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1016\/S0042-6989(03)00457-7","article-title":"Visual perception in a blind subject with a chronic microelectronic retinal prosthesis","volume":"43","author":"Humayun","year":"2003","journal-title":"Vis. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.preteyeres.2013.09.002","article-title":"Using human induced pluripotent stem cells to treat retinal disease","volume":"37","author":"Borooah","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.01.004","article-title":"Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases","volume":"58","author":"Jones","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41433-018-0061-z","article-title":"Cellular regeneration strategies for macular degen-eration: Past, present and future","volume":"32","author":"Chichagova","year":"2018","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.tibtech.2017.06.016","article-title":"Stem Cell Therapies for Reversing Vision Loss","volume":"35","author":"Higuchi","year":"2017","journal-title":"Trends Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molmed.2015.12.007","article-title":"Cell-Based Therapy for Degenerative Retinal Disease","volume":"22","author":"Zarbin","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","article-title":"Autologous Induced Stem-Cell-Derived Reti-nal Cells for Macular Degeneration","volume":"376","author":"Mandai","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pig-ment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: Follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.stemcr.2015.04.005","article-title":"Treatment of Macular Degeneration Using Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Preliminary Results in Asian Patients","volume":"4","author":"Song","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/bjo.2009.176305","article-title":"Human retinal pigment epithelium (RPE) transplantation: Outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study","volume":"95","author":"Krebs","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.ophtha.2018.04.037","article-title":"Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration","volume":"125","author":"Mehat","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0140-6736(12)60028-2","article-title":"Embryonic stem cell trials for macular degeneration: A preliminary report","volume":"379","author":"Schwartz","year":"2012","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"972","DOI":"10.3389\/fbioe.2020.00972","article-title":"Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do","volume":"8","author":"Ribitsch","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00417-011-1617-9","article-title":"The parameters of the porcine eyeball","volume":"249","author":"Sanchez","year":"2011","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_20","first-page":"1246","article-title":"Altered light responses of single rod photoreceptors in transgenic pigs expressing P347L or P347S rhodopsin","volume":"11","author":"Kraft","year":"2005","journal-title":"Mol. Vis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nbt1097-965","article-title":"Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa","volume":"15","author":"Petters","year":"1997","journal-title":"Nat. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1167\/iovs.11-8784","article-title":"Generation of an Inbred Miniature Pig Model of Retinitis Pigmentosa","volume":"53","author":"Ross","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","first-page":"808","article-title":"Rhodopsin transgenic pigs as a model for human retinitis pigmentosa","volume":"39","author":"Li","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","first-page":"6","article-title":"An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa","volume":"7","author":"Shaw","year":"2001","journal-title":"Mol. Vis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1167\/iovs.16-19355","article-title":"A Swine Model of Selective Geographic Atrophy of Outer Retinal Layers Mimicking Atrophic AMD: A Phase I Escalating Dose of Subretinal Sodium Iodate","volume":"57","author":"Leiva","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/stem.637","article-title":"Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina","volume":"29","author":"Zhou","year":"2011","journal-title":"Stem Cells"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/02713680902936148","article-title":"Rescue from light-induced retinal degeneration by human fetal retinal transplantation in minipigs","volume":"34","author":"Li","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1001\/archopht.123.10.1385","article-title":"Retinal progenitor cell xenografts to the pig retina: Morphologic integration and cytochemical differentiation","volume":"123","author":"Warfvinge","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1089\/clo.2008.0010","article-title":"Isolation of Progenitor Cells from GFP-Transgenic Pigs and Transplantation to the Retina of Allorecipients","volume":"10","author":"Klassen","year":"2008","journal-title":"Cloning Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1634\/stemcells.2006-0541","article-title":"Progenitor Cells from the Porcine Neural Retina Express Photoreceptor Markers after Transplantation to the Subretinal Space of Allorecipients","volume":"25","author":"Klassen","year":"2007","journal-title":"Stem Cells"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s00417-006-0437-9","article-title":"Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa","volume":"245","author":"Ghosh","year":"2007","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"939801","DOI":"10.1155\/2012\/939801","article-title":"Photoreceptor Differentiation following Trans-plantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig","volume":"2012","author":"Klassen","year":"2012","journal-title":"Stem Cells Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3928\/23258160-20160324-07","article-title":"An Innovative Surgical Technique for Sub-retinal Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium in Yucatan Mini Pigs: Preliminary Results","volume":"47","author":"Koss","year":"2016","journal-title":"Ophthalmic Surg. Lasers Imaging Retina"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s00417-016-3386-y","article-title":"Subretinal implantation of a monolayer of hu-man embryonic stem cell-derived retinal pigment epithelium: A feasibility and safety study in Yucat\u00e1n minipigs","volume":"254","author":"Koss","year":"2016","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11791","DOI":"10.1038\/srep11791","article-title":"Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: A pilot study","volume":"5","author":"Sohn","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"AMD143","DOI":"10.1167\/iovs.18-24245","article-title":"An Acute Injury Model for the Phenotypic Char-acteristics of Geographic Atrophy","volume":"59","author":"Bhutto","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1167\/iovs.16-21229","article-title":"Subretinal Glial Membranes in Eyes with Geographic Atrophy","volume":"58","author":"Edwards","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12005","DOI":"10.1073\/pnas.0704756104","article-title":"Essential role for MFG-E8 as ligand for \u03b1v\u03b25 integrin in diurnal retinal phagocytosis","volume":"104","author":"Nandrot","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/jamaophthalmol.2018.1544","article-title":"Efficacy and Safety of Lampalizumab for Geographic At-rophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials","volume":"136","author":"Holz","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1016\/S0161-6420(99)90340-8","article-title":"Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration","volume":"106","author":"Sunness","year":"1999","journal-title":"Ophthalmology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jneuroim.2012.10.007","article-title":"Autoimmune Responses against Photoreceptor Antigens during Retinal Degeneration and Their Role in Macrophage Recruitment into Retinas of RCS Rats","volume":"254","author":"Kyger","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Romero-Vazquez, S., Llorens, V., Soler-Boronat, A., Figueras-Roca, M., Adan, A., and Molins, B. (2021). Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070763"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.10703","article-title":"Retinal Remodeling Triggered by Photoreceptor Degenerations","volume":"464","author":"Jones","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1442-9071.1982.tb00366.x","article-title":"Drusen Patterns Predisposing to Geographic Atrophy of the Retinal Pigment Epithelium","volume":"10","author":"Sarks","year":"1982","journal-title":"Aust. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1001\/archopht.1990.01070120090035","article-title":"Relationship of Drusen and Abnormalities of the Retinal Pigment Epithelium to the Prognosis of Neovascular Macular Degeneration. The Macular Photocoagulation Study Group","volume":"108","author":"Bressler","year":"1990","journal-title":"Arch. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"jcs215798","DOI":"10.1242\/jcs.215798","article-title":"In Vitro Drusen Model - Three-Dimensional Spheroid Culture of Retinal Pigment Epithelial Cells","volume":"132","author":"Usui","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nm.3457","article-title":"Cell-to-Cell Transmission of Pathogenic Proteins in Neurodegenerative Diseases","volume":"20","author":"Guo","year":"2014","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-17121-0_1","article-title":"Apolipoprotein E Isoforms and AMD","volume":"854","author":"Toops","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1091\/mbc.e14-05-1028","article-title":"Cholesterol-Mediated Activation of Acid Sphingomyelinase Disrupts Autophagy in the Retinal Pigment Epithelium","volume":"26","author":"Toops","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_50","first-page":"2988","article-title":"A2E, a Lipofuscin Fluorophore, in Human Retinal Pigmented Epithelial Cells in Culture","volume":"40","author":"Sparrow","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-1-4615-0067-4_26","article-title":"A2E, a Fluorophore of RPE Lipofuscin: Can It Cause RPE Degeneration?","volume":"533","author":"Sparrow","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_52","first-page":"416","article-title":"The Fate of the Phagosome: Conversion to \u201cage Pigment\u201d and Impact in Human Retinal Pigment Epithelium","volume":"103","author":"Eldred","year":"1983","journal-title":"Trans. Ophthalmol. Soc. UK"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eaat5580","DOI":"10.1126\/scitranslmed.aat5580","article-title":"Clinical-Grade Stem Cell-Derived Retinal Pigment Epithelium Patch Rescues Retinal Degeneration in Rodents and Pigs","volume":"11","author":"Sharma","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1167\/iovs.03-0662","article-title":"Survival of Allogeneic Porcine Retinal Pigment Epithelial Sheets after Subretinal Transplantation","volume":"45","author":"Tezel","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1089\/scd.2013.0471","article-title":"Migration, Integration and Maturation of Photoreceptor Precursors Following Transplantation in the Mouse Retina","volume":"23","author":"Barber","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","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":"ref_57","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exer.2013.12.018","article-title":"Barrier Properties of Cultured Retinal Pigment Epithelium","volume":"126","author":"Rizzolo","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1038\/mtm.2016.10","article-title":"Comparative Study of Human Embryonic Stem Cells (HESC) and Human Induced Pluripotent Stem Cells (HiPSC) as a Treatment for Retinal Dystrophies","volume":"3","author":"Riera","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.omtm.2021.02.006","article-title":"Cell Therapy with Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium and Retinal Precursor Cells Prevents Visual Function Loss in a Rat Model of Retinal Degeneration","volume":"20","author":"Salas","year":"2021","journal-title":"Mol. Ther.-Methods Clin. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"121049","DOI":"10.1016\/j.biomaterials.2021.121049","article-title":"Repopulation of Decellularized Retinas with HiPSC-Derived Retinal Pigment Epithelial and Ocular Progenitor Cells Shows Cell Engraftment, Organization and Differentiation","volume":"276","author":"Maqueda","year":"2021","journal-title":"Biomaterials"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The Retinal Pigment Epithelium in Visual Function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1167\/iovs.16-20738","article-title":"Integration of Subretinal Suspension Transplants of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in a Large-Eyed Model of Geographic Atrophy","volume":"58","author":"Bartuma","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","first-page":"9","article-title":"Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model","volume":"6","author":"Antonsson","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9428176","DOI":"10.1155\/2017\/9428176","article-title":"Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models","volume":"2017","author":"Lin","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nbt0708-739","article-title":"HLA-Haplotype Banking and IPS Cells","volume":"26","author":"Nakatsuji","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.stem.2009.09.008","article-title":"Generation of Induced Pluripotent Stem Cells from Human Cord Blood Using OCT4 and SOX2","volume":"5","author":"Giorgetti","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"108424","DOI":"10.1016\/j.exer.2020.108424","article-title":"Transcriptomics Analysis of Ccl2\/Cx3cr1\/Crb1rd8 Deficient Mice Provides New Insights into the Pathophysiology of Progressive Retinal Degeneration","volume":"203","author":"Badia","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1084\/jem.20041447","article-title":"Loss of Synchronized Retinal Phagocytosis and Age-Related Blindness in Mice Lacking Alphavbeta5 Integrin","volume":"200","author":"Nandrot","year":"2004","journal-title":"J. Exp. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:58Z","timestamp":1760166418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":68,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910497"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910497","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}