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Posterior Segment

Treatment of Age-Related Macular Degeneration with Pluripotent Stem Cell-Derived Retinal Pigment Epithelium

ORCID Icon, ORCID Icon &
Pages 361-371 | Received 06 Sep 2019, Accepted 01 Nov 2019, Published online: 28 Nov 2019

References

  • Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–116. doi:10.1016/S2214-109X(13)70145-1.
  • Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol. 2012;96(5):752–56. doi:10.1136/bjophthalmol-2011-301109.
  • Blind R The cost of sight loss in the UK. Campaign Report No 23 2004.
  • Pezzullo L, Streatfeild J, Simkiss P, Shickle D. The economic impact of sight loss and blindness in the UK adult population. BMC Health Serv Res. 2018;18(1):63. doi:10.1186/s12913-018-2836-0.
  • Rizzolo LJ, Peng S, Luo Y, Xiao W. Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium. Prog Retin Eye Res. 2011;30(5):296–323. doi:10.1016/j.preteyeres.2011.06.002.
  • Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85(3):845–81. doi:10.1152/physrev.00021.2004.
  • Bharti K, Nguyen MT, Skuntz S, Bertuzzi S, Arnheiter H. The other pigment cell: specification and development of the pigmented epithelium of the vertebrate eye. Pigment Cell Res. 2006;19(5):380–94. doi:10.1111/pcr.2006.19.issue-5.
  • Marshall J. The ageing retina: physiology or pathology. Eye (Lond). 1987;1(2):282–95. doi:10.1038/eye.1987.47.
  • Kinnunen K, Petrovski G, Moe MC, Berta A, Kaarniranta K. Molecular mechanisms of retinal pigment epithelium damage and development of age-related macular degeneration. Acta Ophthalmol. 2012;90(4):299–309. doi:10.1111/j.1755-3768.2011.02179.x.
  • Ramrattan RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, de Jong PT. Morphometric analysis of bruch’s membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci. 1994;35:2857–64.
  • Curcio CA, Johnson M. Structure, function, and pathology of bruch’s membrane. Retina 5th ed. Amsterdam, Netherlands: Elsevier Inc; 2012. p. 465–481.
  • Kamei M, Hollyfield JG. Timp-3 in bruch’s membrane: changes during aging and in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1999;40:2367–75.
  • Chong NH, Keonin J, Luthert PJ, Frennesson CI, Weingeist DM, Wolf RL, Mullins RF, Hageman GS. Decreased thickness and integrity of the macular elastic layer of bruch’s membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol. 2005;166(1):241–51. doi:10.1016/S0002-9440(10)62248-1.
  • Huang JD, Presley JB, Chimento MF, Curcio CA, Johnson M. Age-related changes in human macular bruch’s membrane as seen by quick-freeze/deep-etch. Exp Eye Res. 2007;85(2):202–18. doi:10.1016/j.exer.2007.03.011.
  • Karwatowski WS, Jeffries TE, Duance VC, Albon J, Bailey AJ, Easty DL. Preparation of bruch’s membrane and analysis of the age-related changes in the structural collagens. Br J Ophthalmol. 1995;79(10):944–52. doi:10.1136/bjo.79.10.944.
  • Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004;122(4):598–614. doi:10.1001/archopht.122.4.598.
  • Curcio CA, Johnson M, Huang JD, Rudolf M. Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein b-containing lipoproteins. Prog Retin Eye Res. 2009;28(6):393–422. doi:10.1016/j.preteyeres.2009.08.001.
  • Ebrahimi KB, Handa JT. Lipids, lipoproteins, and age-related macular degeneration. J Lipids. 2011;2011:802059. doi:10.1155/2011/802059.
  • Li CM, Chung BH, Presley JB, Malek G, Zhang X, Dashti N, Li L, Chen J, Bradley K, Kruth HS, et al. Lipoprotein-like particles and cholesteryl esters in human bruch’s membrane: initial characterization. Invest Ophthalmol Vis Sci. 2005;46(7):2576–86. doi:10.1167/iovs.05-0034.
  • Pauleikhoff D, Sheraidah G, Marshall J, Bird AC, Wessing A. [Biochemical and histochemical analysis of age related lipid deposits in bruch’s membrane]. Ophthalmologe. 1994;91:730–34.
  • Bird AC, Marshall J. Retinal-pigment epithelial detachments in the elderly. Trans Ophthalmol Soc U K. 1986;105:674–82.
  • Ruberti JW, Curcio CA, Millican CL, Menco BPM, Huang JD, Johnson M. Quick-freeze/deep-etch visualization of age-related lipid accumulation in bruch’s membrane. Invest Ophthalmol Vis Sci. 2003;44(4):1753–59. doi:10.1167/iovs.02-0496.
  • Hussain AA, Starita C, Hodgetts A, Marshall J. Macromolecular diffusion characteristics of ageing human bruch’s membrane: implications for age-related macular degeneration (amd). Exp Eye Res. 2010;90(6):703–10. doi:10.1016/j.exer.2010.02.013.
  • Moore DJ, Clover GM. The effect of age on the macromolecular permeability of human bruch’s membrane. Invest Ophthalmol Vis Sci. 2001;42:2970–75.
  • Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BE. The epidemiology of retinal reticular drusen. Am J Ophthalmol. 2008;145(2):317–26. doi:10.1016/j.ajo.2007.09.008.
  • Zweifel SA, Imamura Y, Spaide TC, Fujiwara T, Spaide RF. Prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) in age-related macular degeneration. Ophthalmology. 2010;117(9):1775–81. doi:10.1016/j.ophtha.2010.01.027.
  • Buch H, Nielsen NV, Vinding T, Jensen GB, Prause JU, la Cour M. 14-year incidence, progression, and visual morbidity of age-related maculopathy: the copenhagen city eye study. Ophthalmology. 2005;112(5):787–98. doi:10.1016/j.ophtha.2004.11.040.
  • Pauleikhoff D, Barondes MJ, Minassian D, Chisholm IH, Bird AC. Drusen as risk-factors in age-related macular disease. Am J Ophthalmol. 1990;109(1):38–43. doi:10.1016/S0002-9394(14)75576-X.
  • Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci. 2016;73:1765–86.
  • Curcio CA, Medeiros NE, Millican CL. Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1996;37:1236–49.
  • Johnson PT, Brown MN, Pulliam BC, Anderson DH, Johnson LV. Synaptic pathology, altered gene expression, and degeneration in photoreceptors impacted by drusen. Invest Ophthalmol Vis Sci. 2005;46(12):4788–95. doi:10.1167/iovs.05-0767.
  • Group CR, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897–908.
  • Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537–48. doi:10.1016/j.ophtha.2012.09.006.
  • Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther. 2016;10:1857–67. doi:10.2147/DDDT.S97653.
  • Gouras P, Flood MT, Kjeldbye H. Transplantation of cultured human retinal cells to monkey retina. An Acad Bras Cienc. 1984;56:431–43.
  • Algvere PV, Berglin L, Gouras P, Sheng Y. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol. 1994;232(12):707–16. doi:10.1007/BF00184273.
  • da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P. Rpe transplantation and its role in retinal disease. Prog Retin Eye Res. 2007;26(6):598–635. doi:10.1016/j.preteyeres.2007.07.001.
  • Lund RD, Adamson P, Sauve Y, Keegan DJ, Girman SV, Wang S, Winton H, Kanuga N, Kwan AS, Beauchene L, et al. Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats. Proc Natl Acad Sci U S A. 2001;98(17):9942–47. doi:10.1073/pnas.171266298.
  • Arnhold S, Heiduschka P, Klein H, Absenger Y, Basnaoglu S, Kreppel F, Henke-Fahle S, Kochanek S, Bartz-Schmidt KU, Addicks K, et al. Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Invest Ophthalmol Vis Sci. 2006;47(9):4121–29. doi:10.1167/iovs.04-1501.
  • Rezai KA, Kohen L, Wiedemann P, Heimann K. Iris pigment epithelium transplantation. Graefes Arch Clin Exp Ophthalmol. 1997;235(9):558–62. doi:10.1007/BF00947084.
  • Rezai KA, Lai WW, Farrokh-Siar L, Pearlman J, Shu J, Patel SC, Ernest JT. A new method of culturing and transferring iris pigment epithelium. Invest Ophthalmol Vis Sci. 1997;38:2255–60.
  • Rezai KA, Lappas A, Farrokh-siar L, Kohen L, Wiedemann P, Heimann K. Iris pigment epithelial cells of long evans rats demonstrate phagocytic activity. Exp Eye Res. 1997;65(1):23–29. doi:10.1006/exer.1997.0307.
  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–47. doi:10.1126/science.282.5391.1145.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76. doi:10.1016/j.cell.2006.07.024.
  • Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, Suemori H, Nakatsuji N, Ide C, Honda Y, et al. In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci. 2004;45(3):1020–25. doi:10.1167/iovs.03-1034.
  • Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa S, et al. Generation of dopaminergic neurons and pigmented epithelia from primate es cells by stromal cell-derived inducing activity. Proc Natl Acad Sci U S A. 2002;99(3):1580–85. doi:10.1073/pnas.032662199.
  • Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R. Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells. 2004;6(3):217–45. doi:10.1089/clo.2004.6.217.
  • Liao JL, Yu J, Huang K, Hu J, Diemer T, Ma Z, Dvash T, Yang XJ, Travis GH, Williams DS, et al. Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cells. Hum Mol Genet. 2010;19(21):4229–38. doi:10.1093/hmg/ddq341.
  • Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauve Y, Lanza R. Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells. 2006;8(3):189–99. doi:10.1089/clo.2006.8.189.
  • Vaajasaari H, Ilmarinen T, Juuti-Uusitalo K, Rajala K, Onnela N, Narkilahti S, Suuronen R, Hyttinen J, Uusitalo H, Skottman H. Toward the defined and xeno-free differentiation of functional human pluripotent stem cell-derived retinal pigment epithelial cells. Mol Vis. 2011;17:558–75.
  • Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A, Lundh P, Semo M, Ahmado A, Gias C, et al. Elucidating the phenomenon of hesc-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol. 2008;214(2):347–61. doi:10.1016/j.expneurol.2008.09.007.
  • Carr AJ, Vugler A, Lawrence J, Chen LL, Ahmado A, Chen FK, Semo M, Gias C, da Cruz L, Moore HD, et al. Molecular characterization and functional analysis of phagocytosis by human embryonic stem cell-derived RPE cells using a novel human retinal assay. Mol Vis. 2009;15:283–95.
  • Schwartz SD, Regillo CD, Lam BL, Eliott D, Rosenfeld PJ, Gregori NZ, Hubschman JP, Davis JL, Heilwell G, Spirn M, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet. 2015;385(9967):509–16. doi:10.1016/S0140-6736(14)61376-3.
  • Bharti K, Gasper M, Ou J, Brucato M, Clore-Gronenborn K, Pickel J, Arnheiter H. A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet. 2012;8(7):e1002757. doi:10.1371/journal.pgen.1002757.
  • Buchholz DE, Pennington BO, Croze RH, Hinman CR, Coffey PJ, Clegg DO. Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium. Stem Cells Transl Med. 2013;2(5):384–93. doi:10.5966/sctm.2012-0163.
  • Carr AJ, Smart MJ, Ramsden CM, Powner MB, da Cruz L, Coffey PJ. Development of human embryonic stem cell therapies for age-related macular degeneration. Trends Neurosci. 2013;36(7):385–95. doi:10.1016/j.tins.2013.03.006.
  • Hirami Y, Osakada F, Takahashi K, Okita K, Yamanaka S, Ikeda H, Yoshimura N, Takahashi M. Generation of retinal cells from mouse and human induced pluripotent stem cells. Neurosci Lett. 2009;458(3):126–31. doi:10.1016/j.neulet.2009.04.035.
  • Kuroda T, Ando S, Takeno Y, Kishino A, Kimura T. Robust induction of retinal pigment epithelium cells from human induced pluripotent stem cells by inhibiting FGF/MAPK signaling. Stem Cell Res. 2019;39:101514. doi:10.1016/j.scr.2019.101514.
  • Leach LL, Buchholz DE, Nadar VP, Lowenstein SE, Clegg DO. Canonical/beta-catenin wnt pathway activation improves retinal pigmented epithelium derivation from human embryonic stem cells. Invest Ophthalmol Vis Sci. 2015;56(2):1002–13. doi:10.1167/iovs.14-15835.
  • Reh TA, Lamba D, Gust J. Directing human embryonic stem cells to a retinal fate. Methods Mol Biol. 2010;636:139–53.
  • Croze RH, Buchholz DE, Radeke MJ, Thi WJ, Hu Q, Coffey PJ, Clegg DO. Rock inhibition extends passage of pluripotent stem cell-derived retinal pigmented epithelium. Stem Cells Transl Med. 2014;3(9):1066–78. doi:10.5966/sctm.2014-0079.
  • Oswald J, Baranov P. Regenerative medicine in the retina: from stem cells to cell replacement therapy. Ther Adv Ophthalmol. 2018;10:2515841418774433.
  • Stacey G, Andrews PW, Asante C, Barbaric I, Barry J, Bisset L, Braybrook J, Buckle R, Chandra A, Coffey P, et al. Science-based assessment of source materials for cell-based medicines: report of a stakeholders workshop. Regen Med. 2018;13(8):935–44. doi:10.2217/rme-2018-0120.
  • Williams DJ, Archer R, Archibald P, Bantounas I, Baptista R, Barker R, Barry J, Bietrix F, Blair N, Braybrook J, et al. Comparability: manufacturing, characterization and controls, report of a UK regenerative medicine platform pluripotent stem cell platform workshop, trinity hall, cambridge, 14–15 september 2015. Regen Med. 2016;11(5):483–92. doi:10.2217/rme-2016-0053.
  • Coffey PJ, Whiteley SJ, Lund RD. Preservation and restoration of vision following transplantation. Prog Brain Res. 2000;127:489–99.
  • Kokkinaki M, Sahibzada N, Golestaneh N. Human induced pluripotent stem-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized vascular endothelial growth factor secretion, and gene expression pattern similar to native RPE. Stem Cells. 2011;29(5):825–35. doi:10.1002/stem.635.
  • de Rham C, Villard J. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy. J Immunol Res. 2014;2014:1–6. doi:10.1155/2014/518135.
  • Fairchild PJ, Horton C, Lahiri P, Shanmugarajah K, Davies TJ. Beneath the sword of damocles: regenerative medicine and the shadow of immunogenicity. Regen Med. 2016;11(8):817–29. doi:10.2217/rme-2016-0134.
  • Robertson NJ, Brook FA, Gardner RL, Cobbold SP, Waldmann H, Fairchild PJ. Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance. Proc Natl Acad Sci U S A. 2007;104(52):20920–25. doi:10.1073/pnas.0710265105.
  • Taylor CJ, Bolton EM, Pocock S, Sharples LD, Pedersen RA, Bradley JA. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet. 2005;366(9502):2019–25. doi:10.1016/S0140-6736(05)67813-0.
  • Xu HG, Wang B, Ono M, Kagita A, Fujii K, Sasakawa N, Ueda T, Gee P, Nishikawa M, Nomura M, et al. Targeted disruption of HLA genes via CRISPR-cas9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell. 2019;24(4):566-+. doi:10.1016/j.stem.2019.02.005.
  • Wilmut I, Leslie S, Martin NG, Peschanski M, Rao M, Trounson A, Turner D, Turner ML, Yamanaka S, Taylor CJ. Development of a global network of induced pluripotent stem cell haplobanks. Regen Med. 2015;10(3):235–38. doi:10.2217/rme.15.1.
  • Noguchi H, Miyagi-Shiohira C, Nakashima Y. Induced tissue-specific stem cells and epigenetic memory in induced pluripotent stem cells. Int J Mol Sci. 2018;19(4):930.
  • Perrera V, Martello G. How does reprogramming to pluripotency affect genomic imprinting? Front Cell Dev Biol. 2019;7. doi:10.3389/fcell.2019.00076.
  • Mandai M, Kurimoto Y, Takahashi M. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;377:792–93.
  • Kamath A, Ternes S, McGowan S, English A, Mallampalli R, AB M. Efficient method to create integration-free, virus-free, myc and lin28-free human induced pluripotent stem cells from adherent cells. Future Sci OA. 2017;3(3):FSO211. doi:10.4155/fsoa-2017-0028.
  • Attwood SW, Edel MJ. iPS-cell technology and the problem of genetic instability-can it ever be safe for clinical use? J Clin Med. 2019;8(3):288. doi:10.3390/jcm8030288.
  • Baker D, Hirst AJ, Gokhale PJ, Juarez MA, Williams S, Wheeler M, Bean K, Allison TF, Moore HD, Andrews PW, et al. Detecting genetic mosaicism in cultures of human pluripotent stem cells. Stem Cell Rep. 2016;7(5):998–1012. doi:10.1016/j.stemcr.2016.10.003.
  • Merkle FT, Ghosh S, Kamitaki N, Mitchell J, Avior Y, Mello C, Kashin S, Mekhoubad S, Ilic D, Charlton M, et al. Human pluripotent stem cells recurrently acquire and expand dominant negative p53 mutations. Nature. 2017;545(7653):229–33. doi:10.1038/nature22312.
  • PD W, Kurihara T, Bravo S, Feitelberg D, Sedillo ZA, Aguilar E, Friedlander M. Performing subretinal injections in rodents to deliver retinal pigment epithelium cells in suspension. J Vis Exp. 2015;95:52247.
  • Stein JD, Zacks DN, Grossman D, Grabe H, Johnson MW, Sloan FA. Adverse events after pars plana vitrectomy among medicare beneficiaries. Arch Ophthalmol. 2009;127(12):1656–63. doi:10.1001/archophthalmol.2009.300.
  • Amer MH, White LJ, Shakesheff KM. The effect of injection using narrow-bore needles on mammalian cells: administration and formulation considerations for cell therapies. J Pharm Pharmacol. 2015;67(5):640–50. doi:10.1111/jphp.2015.67.issue-5.
  • Diniz B, Thomas P, Thomas B, Ribeiro R, Hu Y, Brant R, Ahuja A, Zhu D, Liu L, Koss M, et al. Subretinal implantation of retinal pigment epithelial cells derived from human embryonic stem cells: improved survival when implanted as a monolayer. Invest Ophthalmol Vis Sci. 2013;54(7):5087–96. doi:10.1167/iovs.12-11239.
  • Nommiste B, Fynes K, Tovell VE, Ramsden C, da Cruz L, Coffey P. Stem cell-derived retinal pigment epithelium transplantation for treatment of retinal disease. Prog Brain Res. 2017;231:225–44.
  • Radeke MJ, Radeke CM, Shih YH, Hu J, Bok D, Johnson LV, Coffey PJ. Restoration of mesenchymal retinal pigmented epithelial cells by TGFβ pathway inhibitors: implications for age-related macular degeneration. Genome Med. 2015;7(1):58. doi:10.1186/s13073-015-0183-x.
  • Hsiung J, Zhu DH, Hinton DR. Polarized human embryonic stem cell-derived retinal pigment epithelial cell monolayers have higher resistance to oxidative stress-induced cell death than nonpolarized cultures. Stem Cells Transl Med. 2015;4(1):10–20. doi:10.5966/sctm.2014-0205.
  • da Cruz L, Fynes K, Georgiadis O, Kerby J, Luo YH, Ahmado A, Vernon A, Daniels JT, Nommiste B, Hasan SM, et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol. 2018;36(4):328–37. doi:10.1038/nbt.4114.
  • Kashani AH, Lebkowski JS, Rahhal FM, Avery RL, Salehi-Had H, Dang W, Lin CM, Mitra D, Zhu D, Thomas BB, et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci Transl Med. 2018;10:435. doi:10.1126/scitranslmed.aao4097.
  • Liu Z, Yu N, Holz FG, Yang F, Stanzel BV. Enhancement of retinal pigment epithelial culture characteristics and subretinal space tolerance of scaffolds with 200 nm fiber topography. Biomaterials. 2014;35(9):2837–50. doi:10.1016/j.biomaterials.2013.12.069.
  • Song MJ, Bharti K. Looking into the future: using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res. 2016;1638:2–14. doi:10.1016/j.brainres.2015.12.011.
  • Kamao H, Mandai M, Okamoto S, Sakai N, Suga A, Sugita S, Kiryu J, Takahashi M. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep. 2014;2(2):205–18. doi:10.1016/j.stemcr.2013.12.007.
  • Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R. Embryonic stem cell trials for macular degeneration: A preliminary report. Lancet. 2012;379(9817):713–20. doi:10.1016/S0140-6736(12)60028-2.
  • Takagi S, Mandai M, Gocho K, Hirami Y, Yamamoto M, Fujihara M, Sugita S, Kurimoto Y, Takahashi M. Evaluation of transplanted autologous induced pluripotent stem cell-derived retinal pigment epithelium in exudative age-related macular degeneration. Ophthalmol Retina. 2019;3:850–59. doi:10.1016/j.oret.2019.04.021.

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