{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:59:35Z","timestamp":1789203575695,"version":"build-2803163510"},"reference-count":100,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T00:00:00Z","timestamp":1481155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The field of stem cell biology has rapidly evolved in the last few decades. In the area of regenerative medicine, clinical applications using stem cells hold the potential to be a powerful tool in the treatment of a wide variety of diseases, in particular, disorders of the eye. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are promising technologies that can potentially provide an unlimited source of cells for cell replacement therapy in the treatment of retinal degenerative disorders such as age-related macular degeneration (AMD), Stargardt disease, and other disorders. ESCs and iPSCs have been used to generate retinal pigment epithelium (RPE) cells and their functional behavior has been tested in vitro and in vivo in animal models. Additionally, iPSC-derived RPE cells provide an autologous source of cells for therapeutic use, as well as allow for novel approaches in disease modeling and drug development platforms. Clinical trials are currently testing the safety and efficacy of these cells in patients with AMD. In this review, the current status of iPSC disease modeling of AMD is discussed, as well as the challenges and potential of this technology as a viable option for cell replacement therapy in retinal degeneration.<\/jats:p>","DOI":"10.3390\/cells5040044","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T10:39:01Z","timestamp":1481193541000},"page":"44","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Potential of Induced Pluripotent Stem Cells (iPSCs) for Treating Age-Related Macular Degeneration (AMD)"],"prefix":"10.3390","volume":"5","author":[{"given":"Mark","family":"Fields","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale School of Medicine, Yale University, 300 George St., Suite 8100, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale School of Medicine, Yale University, 300 George St., Suite 8100, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale School of Medicine, Yale University, 300 George St., Suite 8100, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian","family":"Del Priore","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale School of Medicine, Yale University, 300 George St., Suite 8100, New Haven, CT 06511, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,8]]},"reference":[{"key":"ref_1","first-page":"74","article-title":"Current Progress of Human Trials Using Stem Cell Therapy as a Treatment for Diabetes Mellitus","volume":"5","author":"Cheng","year":"2016","journal-title":"Am. J. Stem Cells"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kumar, A., Narayanan, K., Chaudhary, R.K., Mishra, S., Kumar, S., Vinoth, K.J., Padmanabhan, P., and Gulyas, B. (2016). Current Perspective of Stem Cell Therapy in Neurodegenerative and Metabolic Diseases. Mol. Neurobiol.","DOI":"10.1007\/s12035-016-0217-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archopht.122.4.564","article-title":"Prevalence of Age-Related Macular Degeneration in the United States","volume":"122","author":"Friedman","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human Embryonic Stem Cell-Derived Retinal Pigment 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":"2014","journal-title":"Lancet"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature11807","article-title":"Negligible Immunogenicity of Terminally Differentiated Cells Derived from Induced Pluripotent or Embryonic Stem Cells","volume":"494","author":"Araki","year":"2013","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.stem.2013.01.006","article-title":"Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells","volume":"12","author":"Guha","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/embj.201387098","article-title":"iPS Cells: A Game Changer for Future Medicine","volume":"33","author":"Inoue","year":"2014","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1756-6606-7-22","article-title":"iPS Cell Technologies: Significance and Applications to CNS Regeneration and Disease","volume":"7","author":"Okano","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/clpt.2011.38","article-title":"The Use of Induced Pluripotent Stem Cells in Drug Development","volume":"89","author":"Inoue","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_12","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":"ref_13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/978-3-319-17121-0_73","article-title":"Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells","volume":"854","author":"Li","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/02713680500514628","article-title":"Bruch Membrane Aging Alters the Gene Expression Profile of Human Retinal Pigment Epithelium","volume":"31","author":"Cai","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1056\/NEJMra0801537","article-title":"Age-Related Macular Degeneration","volume":"358","author":"Jager","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0039-6257(88)90052-5","article-title":"Age-Related Macular Degeneration","volume":"32","author":"Bressler","year":"1988","journal-title":"Surv. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/00006982-198808020-00005","article-title":"Drusen Characteristics in Patients with Exudative Versus Non-Exudative Age-Related Macular Degeneration","volume":"8","author":"Bressler","year":"1988","journal-title":"Retina"},{"key":"ref_18","unstructured":"Zinn, K.M., and Marmor, M.F. (1979). The Retinal Pigment Epithelium, Harvard University Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/S0161-6420(82)34613-8","article-title":"Clinical-Ultrastructural Study of Thioridazine Retinopathy","volume":"89","author":"Miller","year":"1982","journal-title":"Ophthalmology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0161-6420(81)35027-1","article-title":"Experimental Model of Gyrate Atrophy in Animals","volume":"88","author":"Kuwabara","year":"1981","journal-title":"Ophthalmology"},{"key":"ref_21","first-page":"444","article-title":"The Relationship between Retinal Pigment Epithelium and the Choriocapillaris","volume":"103","author":"Henkind","year":"1983","journal-title":"Trans. Ophthalmol. Soc. U. K."},{"key":"ref_22","first-page":"1135","article-title":"RPE Destruction Causes Choriocapillary Atrophy","volume":"25","author":"Korte","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","first-page":"161","article-title":"Retinal Degeneration after Intravitreal Injection of Ornithine. 2. Late Change after Administration","volume":"96","author":"Takeuchi","year":"1992","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"ref_24","first-page":"17","article-title":"Changes in the Intermediate Stage of Retinal Degeneration after Intravitreal Injection of Ornithine","volume":"97","author":"Takeuchi","year":"1993","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1136\/bjo.81.6.481","article-title":"Decreased Choriocapillaris Perfusion Following Surgical Excision of Choroidal Neovascular Membranes in Age-Related Macular Degeneration","volume":"81","author":"Nasir","year":"1997","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1136\/bjo.80.4.314","article-title":"Postoperative Abnormalities of the Choriocapillaris in Exudative Age-Related Macular Degeneration","volume":"80","author":"Pollack","year":"1996","journal-title":"Br. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1001\/archopht.1995.01100040023014","article-title":"Choriocapillaris Atrophy after Submacular Surgery in Presumed Ocular Histoplasmosis Syndrome","volume":"113","author":"Desai","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_28","first-page":"1094","article-title":"Clinicopathologic Correlation of Localized Retinal Pigment Epithelium Debridement","volume":"38","author":"Leonard","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1001\/archopht.1995.01100070113034","article-title":"Debridement of the Pig Retinal Pigment Epithelium In Vivo","volume":"113","author":"Hornbeck","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1001\/archopht.1995.01100070106033","article-title":"Retinal Pigment Epithelial Repopulation in Monkeys after Submacular Surgery","volume":"113","author":"Valentino","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0002-9394(14)70481-7","article-title":"Retinal Pigment Epithelial Debridement as a Model for the Pathogenesis and Treatment of Macular Degeneration","volume":"122","author":"Kaplan","year":"1996","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","unstructured":"Stephen, H.T. (2013). Stem Cell Biology and Regenerative Medicine in Ophthalmology, Springer."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.phrs.2015.11.027","article-title":"Targeting VEGF in Eye Neovascularization: What\u2019s New?: A Comprehensive Review on Current Therapies and Oligonucleotide-Based Interventions under Development","volume":"103","author":"Amadio","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0161-6420(90)32619-2","article-title":"Aging Changes in Bruch\u2019s Membrane. A Histochemical and Morphologic Study","volume":"97","author":"Pauleikhoff","year":"1990","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1136\/bjo.83.3.358","article-title":"Early Drusen Formation in the Normal and Aging Eye and Their Relation to Age Related Maculopathy: A Clinicopathological Study","volume":"83","author":"Sarks","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_36","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\u2019s 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":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0039-6257(99)00072-7","article-title":"Drusen in Age-Related Macular Degeneration: Pathogenesis, Natural Course, and Laser Photocoagulation-Induced Regression","volume":"44","author":"Abdelsalam","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/eye.2001.142","article-title":"Structure and Composition of Drusen Associated with Glomerulonephritis: Implications for the Role of Complement Activation in Drusen Biogenesis","volume":"15","author":"Mullins","year":"2001","journal-title":"Eye"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1136\/bjophthalmol-2011-300344","article-title":"The Oil Spill in Ageing Bruch Membrane","volume":"95","author":"Curcio","year":"2011","journal-title":"Br. J. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1136\/bjo.76.10.607","article-title":"Type IV Collagen and Laminin in Bruch\u2019s Membrane and Basal Linear Deposit in the Human Macula","volume":"76","author":"Marshall","year":"1992","journal-title":"Br. J. Ophthalmol."},{"key":"ref_41","first-page":"907","article-title":"Extracellular Matrix Alterations Precede Vascularization of the Retinal Pigment Epithelium in Dystrophic Rats","volume":"8","author":"Caldwell","year":"1989","journal-title":"Curr. Eye Res."},{"key":"ref_42","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\u2019s Membrane","volume":"116","author":"Tezel","year":"1998","journal-title":"Arch. Ophthalmol."},{"key":"ref_43","first-page":"1110","article-title":"Reattachment of Cultured Human Retinal Pigment Epithelium to Extracellular Matrix and Human Bruch\u2019s Membrane","volume":"38","author":"Ho","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","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":"ref_45","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000055532","article-title":"TGF Beta Secretion Modulates the Density-Dependent Growth of Pig Retinal Pigment Epithelium In Vitro","volume":"31","author":"Tezel","year":"1999","journal-title":"Ophthalmic. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.exer.2004.09.006","article-title":"Impaired RPE Survival on Aged Submacular Human Bruch\u2019s Membrane","volume":"80","author":"Gullapalli","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exer.2003.09.024","article-title":"Short-Term Study of Retinal Pigment Epithelium Sheet Transplants onto Bruch\u2019s Membrane","volume":"78","author":"Wang","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_48","first-page":"767","article-title":"Repopulation of Different Layers of Host Human Bruch\u2019s Membrane by Retinal Pigment Epithelial Cell Grafts","volume":"40","author":"Tezel","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1006\/exer.1997.0404","article-title":"In Vitro Transplantation of Fetal Human Retinal Pigment Epithelial Cells onto Human Cadaver Bruch\u2019s Membrane","volume":"66","author":"Castellarin","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.4.5.10","article-title":"Reengineering Human Bruch\u2019s Membrane Increases Rod Outer Segment Phagocytosis by Human Retinal Pigment Epithelium","volume":"4","author":"Moreira","year":"2015","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_51","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":"ref_52","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1167\/iovs.02-0813","article-title":"Novel Role for a Complement Regulatory Protein (CD46) in Retinal Pigment Epithelial Adhesion","volume":"44","author":"McLaughlin","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1167\/iovs.04-0193","article-title":"Reengineering of Aged Bruch\u2019s Membrane to Enhance Retinal Pigment Epithelium Repopulation","volume":"45","author":"Tezel","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"9414","DOI":"10.1016\/j.actbio.2013.07.029","article-title":"Primordium of an Artificial Bruch\u2019s Membrane Made of Nanofibers for Engineering of Retinal Pigment Epithelium Cell Monolayers","volume":"9","author":"Warnke","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1167\/iovs.12-11239","article-title":"Subretinal Implantation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer","volume":"54","author":"Diniz","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.stemcr.2015.11.008","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":"Reyes","year":"2016","journal-title":"Stem Cell Reports"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.stem.2008.11.013","article-title":"Generation of Induced Pluripotent Stem Cell Lines from Adult Rat Cells","volume":"4","author":"Liao","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/mrd.21117","article-title":"Generation of Canine Induced Pluripotent Stem Cells by Retroviral Transduction and Chemical Inhibitors","volume":"77","author":"Shimada","year":"2010","journal-title":"Mol. Reprod. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2008.10.014","article-title":"Generation of Induced Pluripotent Stem Cells from Adult Rhesus Monkey Fibroblasts","volume":"3","author":"Liu","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13045-014-0050-z","article-title":"Advances in Understanding the Cell Types and Approaches Used for Generating Induced Pluripotent Stem Cells","volume":"7","author":"Li","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1164270","article-title":"Generation of Mouse Induced Pluripotent Stem Cells without Viral Vectors","volume":"322","author":"Okita","year":"2008","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cell.2009.03.034","article-title":"A Fresh Look at iPS Cells","volume":"137","author":"Yamanaka","year":"2009","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2361763","DOI":"10.1155\/2016\/2361763","article-title":"Induced Pluripotent Stem Cells: Development in the Ophthalmologic Field","volume":"2016","author":"Wu","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.ajo.2006.12.007","article-title":"Adult Retinal Pigment Epithelial Transplantation in Exudative Age-Related Macular Degeneration","volume":"143","author":"Tezel","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S0002-9394(00)00850-3","article-title":"Retinal Pigment Epithelial Cell Transplantation after Subfoveal Membranectomy in Age-Related Macular Degeneration: Clinicopathologic Correlation","volume":"131","author":"Kaplan","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_68","first-page":"ORSFc1-9","article-title":"Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years","volume":"57","author":"Schwartz","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gong, J., Fields, M.A., Moreira, E.F., Bowrey, H.E., Gooz, M., Ablonczy, Z., and Del Priore, L.V. (2015). Differentiation of Human Protein-Induced Pluripotent Stem Cells toward a Retinal Pigment Epithelial Cell Fate. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143272"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/stem.189","article-title":"Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells","volume":"27","author":"Buchholz","year":"2009","journal-title":"Stem Cells"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Carr, A.J., Vugler, A.A., Hikita, S.T., Lawrence, J.M., Gias, C., Chen, L.L., Buchholz, D.E., Ahmado, A., Semo, M., and Smart, M.J. (2009). Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008152"},{"key":"ref_72","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","first-page":"e52214","article-title":"Efficient Derivation of Retinal Pigment Epithelium Cells from Stem Cells","volume":"97","author":"Westenskow","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.1167\/iovs.11-8129","article-title":"Induction of Retinal Pigment Epithelial Cells from Monkey iPS Cells","volume":"52","author":"Okamoto","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.stemcr.2013.12.007","article-title":"Characterization of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Sheets Aiming for Clinical Application","volume":"2","author":"Kamao","year":"2014","journal-title":"Stem Cell Reports"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/bs.pmbts.2015.06.004","article-title":"Retinoid Processing in Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cultures","volume":"134","author":"Fields","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.2119\/molmed.2012.00242","article-title":"Long-Term Safety and Efficacy of Human-Induced Pluripotent Stem Cell (iPS) Grafts in a Preclinical Model of Retinitis Pigmentosa","volume":"18","author":"Li","year":"2012","journal-title":"Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8470263","DOI":"10.1155\/2016\/8470263","article-title":"iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study","volume":"2016","author":"Westenskow","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.csbj.2015.05.001","article-title":"Using Stem Cells to Model Diseases of the Outer Retina","volume":"13","author":"Yvon","year":"2015","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/hmg\/dds469","article-title":"iPS Cell Modeling of Best Disease: Insights into the Pathophysiology of an Inherited Macular Degeneration","volume":"22","author":"Singh","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_81","first-page":"161","article-title":"Duplication of TBK1 Stimulates Autophagy in iPSC-Derived Retinal Cells from a Patient with Normal Tension Glaucoma","volume":"3","author":"Tucker","year":"2014","journal-title":"J. Stem Cell Res. Ther."},{"key":"ref_82","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":"ref_83","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1038\/mt.2014.100","article-title":"Gene Therapy in Patient-Specific Stem Cell Lines and a Preclinical Model of Retinitis Pigmentosa with Membrane Frizzled-Related Protein Defects","volume":"22","author":"Li","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ajo.2003.11.069","article-title":"The Epidemiology of Age-Related Macular Degeneration","volume":"137","author":"Klein","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_85","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":"ref_86","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.genom.9.081307.164350","article-title":"Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration","volume":"10","author":"Swaroop","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.retram.2016.04.001","article-title":"Human Induced Pluripotent Stem Cells: A Disruptive Innovation","volume":"64","author":"Bouckenheimer","year":"2016","journal-title":"Curr. Res. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nrd4738","article-title":"Current Status of Pluripotent Stem Cells: Moving the First Therapies to the Clinic","volume":"14","author":"Kimbrel","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1517\/14712598.2016.1093110","article-title":"Stem Cells in Clinical Trials for Treatment of Retinal Degeneration","volume":"16","author":"Klassen","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/j.1460-9568.2011.07970.x","article-title":"Transplantation of Human Central Nervous System Stem Cells - Neuroprotection in Retinal Degeneration","volume":"35","author":"McGill","year":"2012","journal-title":"Eur. J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3390\/jcm4010159","article-title":"Design of a Tumorigenicity Test for Induced Pluripotent Stem Cell (iPSC)-Derived Cell Products","volume":"4","author":"Kawamata","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/513287a","article-title":"Japan Stem-Cell Trial Stirs Envy","volume":"513","author":"Reardon","year":"2014","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yoshihara, M., Hayashizaki, Y., and Murakawa, Y. (2016). Genomic Instability of iPSCs: Challenges Towards Their Clinical Applications. Stem Cell Rev.","DOI":"10.1007\/s12015-016-9680-6"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nm0216-116","article-title":"An Eye to the Future: Researchers Debate Best Path for Stem Cell-Derived Therapies","volume":"22","author":"Chakradhar","year":"2016","journal-title":"Nat. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nbt0915-890","article-title":"Riken Suspends First Clinical Trial Involving Induced Pluripotent Stem Cells","volume":"33","author":"Garber","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.stemcr.2016.08.010","article-title":"Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in Mhc-Matched Models","volume":"7","author":"Sugita","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.stemcr.2016.08.011","article-title":"Lack of T Cell Response to iPSC-Derived Retinal Pigment Epithelial Cells from HLA Homozygous Donors","volume":"7","author":"Sugita","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_98","unstructured":"Riken to Resume Retinal iPS Transplant Study in Cooperation with Kyoto University. Available online: http:\/\/www.japantimes.co.jp\/news\/2016\/06\/07\/national\/science-health\/riken-resume-retinal-iPS-transplantation-cooperation-kyoto-university\/#.WEdkwH_YWpo."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kanemura, H., Go, M.J., Shikamura, M., Nishishita, N., Sakai, N., Kamao, H., Mandai, M., Morinaga, C., Takahashi, M., and Kawamata, S. (2014). Tumorigenicity Studies of Induced Pluripotent Stem Cell (iPSC)-Derived Retinal Pigment Epithelium (RPE) for the Treatment of Age-Related Macular Degeneration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085336"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nrm.2016.10","article-title":"Pluripotent Stem Cells Progressing to the Clinic","volume":"17","author":"Trounson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/5\/4\/44\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:13Z","timestamp":1760210893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/5\/4\/44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,8]]},"references-count":100,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["cells5040044"],"URL":"https:\/\/doi.org\/10.3390\/cells5040044","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,8]]}}}