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Human Pluripotent Stem Cells as In Vitro Models for Retinal Development and Disease

  • Akshayalakshmi Sridhar
  • Kirstin B. Langer
  • Clarisse M. Fligor
  • Matthew Steinhart
  • Casey A. Miller
  • Kimberly T. Ho-A-Lim
  • Sarah K. Ohlemacher
  • Jason S. MeyerEmail author
Chapter
Part of the Fundamental Biomedical Technologies book series (FBMT)

Abstract

Human pluripotent stem cells (hPSCs) provide unprecedented access to the earliest stages of retinogenesis that remain inaccessible to investigation, thereby serving as powerful tools for studies of retinal development. Additionally, the ability to derive hPSCs from patient sources allows for the modeling of retinal degenerative diseases in vitro, with the potential to facilitate cell replacement strategies in advanced stages of disease. For these purposes, many studies over the past several years have directed the differentiation of hPSCs to generate retinal cells using stochastic methods of differentiation, yielding all major cell types of the retina. In particular, these studies have favored the derivation of RPE, photoreceptors, and more recently retinal ganglion cells for disease modeling, drug screening as well as cell replacement purposes. More recently, advances in retinal differentiation methods have led to the generation of three-dimensional retinal organoids that recapitulate key developmental and morphological features of the retina, including the stratified organization of retinal cells into a tissue-like structure. This review provides an overview of retinal differentiation from hPSCs and their potential use for studies of retinogenesis as well as diseases that affect the retina.

Keywords

Human pluripotent stem cells Retina Organoids Development Disease 

References

  1. 1.
    Barnstable, C. J. (1987). A molecular view of vertebrate retinal development. Molecular Neurobiology, 1, 9–46.PubMedGoogle Scholar
  2. 2.
    Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.Google Scholar
  3. 3.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.  https://doi.org/10.1016/j.cell.2007.11.019 PubMedPubMedCentralGoogle Scholar
  4. 4.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.  https://doi.org/10.1016/j.cell.2006.07.024 PubMedPubMedCentralGoogle Scholar
  5. 5.
    Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917–1920.  https://doi.org/10.1126/science.1151526 PubMedGoogle Scholar
  6. 6.
    Burnight, E. R., Wiley, L.A., Drack, A.V., Braun, T.A., Anfinson, K.R., Kaalberg, E.E., et al. (2014). CEP290 gene transfer rescues Leber congenital amaurosis cellular phenotype. Gene Therapy, 21, 662–672.  https://doi.org/10.1186/1756-6606-7-45 PubMedPubMedCentralGoogle Scholar
  7. 7.
    Carr, A. J., Vugler, A.A., Hikita, S.T., Lawrence, J.M., Gias, C., Chen, L.L., et al. (2009). Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One, 4, e8152.  https://doi.org/10.1371/journal.pone.0008152 PubMedPubMedCentralGoogle Scholar
  8. 8.
    Gonzalez-Cordero, A., Kruczek, K., Naeem, A., Fernando, M., Kloc, M., Ribeiro, J., et al. (2017). Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors. Stem Cell Reports, 9(3), 820–837. https://doi.org/10.1016/j.stemcr.2017.07.022 PubMedPubMedCentralGoogle Scholar
  9. 9.
    Lamba, D. A., McUsic, A., Hirata, R. K., Wang, P. R., Russell, D., & Reh, T. A. (2010). Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS One, 5, e8763.  https://doi.org/10.1371/journal.pone.0008763 PubMedPubMedCentralGoogle Scholar
  10. 10.
    Li, Y., Tsai, Y.T., Hsu, C.W., Erol, D., Yang, J., Wu, W.H., et al. (2012). Long-term safety and efficacy of human-induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa. Molecular Medicine, 18, 1312–1319.  https://doi.org/10.2119/molmed.2012.00242
  11. 11.
    Lukovic, D., Artero Castro, A., Delgado, A.B., Bernal Mde, L., Luna Pelaez, N., Diez Lloret, A., et al. (2015). Human iPSC derived disease model of MERTK-associated retinitis pigmentosa. Scientific Reports, 5, 12910.  https://doi.org/10.1016/j.trsl.2015.08.007 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Pearson, R. A. (2014). Advances in repairing the degenerate retina by rod photoreceptor transplantation. Biotechnology Advances, 32, 485–491.  https://doi.org/10.1016/j.biotechadv.2014.01.001 PubMedPubMedCentralGoogle Scholar
  13. 13.
    Rowland, T. J., Buchholz, D. E., & Clegg, D. O. (2012). Pluripotent human stem cells for the treatment of retinal disease. Journal of Cellular Physiology, 227, 457–466.  https://doi.org/10.1002/jcp.22814 PubMedGoogle Scholar
  14. 14.
    Schwartz, S. D., Hubschman, J.P., Heilwell, G., Franco-Cardenas, V., Pan, C.K., Ostrick, R.M., et al. (2012). Embryonic stem cell trials for macular degeneration: A preliminary report. Lancet, 379, 713–720.  https://doi.org/10.1016/s0140-6736(12)60028-2 Google Scholar
  15. 15.
    Tsai, Y., Lu, B., Bakondi, B., Girman, S., Sahablan, A., Sareen, D., et al. (2015). Human iPSC-derived neural progenitors preserve vision in an amd-like model. Stem Cells (Dayton, OH), 33, 2537–2549.  https://doi.org/10.1002/stem.2032 PubMedPubMedCentralGoogle Scholar
  16. 16.
    Banin, E., Obolensky, A., Idelson, M., Hemo, I., Reinhardtz, E., Pikarsky, E., et al. (2006). Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem cells. Stem Cells (Dayton, OH), 24, 246–257.  https://doi.org/10.1634/stemcells.2005-0009 PubMedPubMedCentralGoogle Scholar
  17. 17.
    Hirami, Y., Osakada, F., Takahashi, K., Okita, K., Yamanaka, S., Ikeda, H., et al. (2009). Generation of retinal cells from mouse and human induced pluripotent stem cells. Neuroscience Letters, 458, 126–131.  https://doi.org/10.1016/j.neulet.2009.04.035 PubMedGoogle Scholar
  18. 18.
    Ikeda, H., Osakada, F., Watanabe, K., Mizuseki, K., Haraguchi, T., Miyoshi, H., et al. (2005). Generation of Rx+/Pax6+ neural retinal precursors from embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 11331–11336.  https://doi.org/10.1073/pnas.0910012107 Google Scholar
  19. 19.
    Lamba, D. A., Karl, M. O., Ware, C. B., & Reh, T. A. (2006). Efficient generation of retinal progenitor cells from human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 103, 12769–12774.  https://doi.org/10.1073/pnas.0601990103 PubMedPubMedCentralGoogle Scholar
  20. 20.
    Mellough, C. B., Sernagor, E., Moreno-Gimeno, I., Steel, D. H., & Lako, M. (2012). Efficient stage specific differentiation of human pluripotent stem cells towards retinal photoreceptor cells. Stem Cells (Dayton, OH).  https://doi.org/10.1002/stem.1037 PubMedGoogle Scholar
  21. 21.
    Meyer, J. S., Howden, S. E., Wallace, K. A., Verhoeven, A. D., Wright, L. S., Capowski, E. E., et al. (2011). Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells (Dayton, OH), 29, 1206–1218.  https://doi.org/10.1002/stem.674 PubMedPubMedCentralGoogle Scholar
  22. 22.
    Meyer, J. S., Shearer, R. L., Capowski, E. E., Wright, L. S., Wallace, K. A., McMillan, E. L., et al. (2009). Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 106, 16698–16703.  https://doi.org/10.1073/pnas.0905245106 Google Scholar
  23. 23.
    Ohlemacher, S. K., Iglesias, C. L., Sridhar, A., Gamm, D. M., & Meyer, J. S. (2015). Generation of highly enriched populations of optic vesicle-like retinal cells from human pluripotent stem cells. Current Protocols in Stem Cell Biology, 32, 1H 8 1–1H 8 20.  https://doi.org/10.1002/9780470151808.sc01h08s32 Google Scholar
  24. 24.
    Osakada, F., Ikeda, H., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., et al. (2008). Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nature Biotechnology, 26, 215–224.  https://doi.org/10.1038/nbt1384 PubMedGoogle Scholar
  25. 25.
    Osakada, F., Ikeda, H., Sasai, Y., & Takahashi, M. (2009). Stepwise differentiation of pluripotent stem cells into retinal cells. Nature Protocols, 4, 811–824.  https://doi.org/10.1038/nprot.2009.51 PubMedGoogle Scholar
  26. 26.
    Sridhar, A., Ohlemacher, S. K., Langer, K. B., & Meyer, J. S. (2016). Robust differentiation of mRNA-reprogrammed human induced pluripotent stem cells toward a retinal lineage. Stem Cells Translational Medicine, 5, 417–426.  https://doi.org/10.5966/sctm.2015-0093 PubMedPubMedCentralGoogle Scholar
  27. 27.
    Sridhar, A., Steward, M. M., & Meyer, J. S. (2013). Nonxenogeneic growth and retinal differentiation of human induced pluripotent stem cells. Stem Cells Translational Medicine, 2, 255–264.  https://doi.org/10.5966/sctm.2012-0101 PubMedPubMedCentralGoogle Scholar
  28. 28.
    Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., et al. (2012). Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell, 10, 771–785.  https://doi.org/10.1016/j.stem.2012.05.009 PubMedGoogle Scholar
  29. 29.
    Phillips, M. J., Wallace, K. A., Dickerson, S. J., Miller, M. J., Verhoeven, A. D., Martin, J. M., et al. (2012). Blood-derived human iPS cells generate optic vesicle-like structures with the capacity to form retinal laminae and develop synapses. Investigative Ophthalmology & Visual Science, 53, 2007–2019.  https://doi.org/10.1167/iovs.11-9313 Google Scholar
  30. 30.
    Zhong, X., Gutierrez, C., Xue, T., Hampton, C., Vergara, M. N., Cao, L. H., et al. (2014). Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nature Communications, 5, 4047.  https://doi.org/10.1038/ncomms5047
  31. 31.
    Kaewkhaw, R., Kaya, K. D., Brooks, M., Homma, K., Zou, J., Chaitankar, V., et al. (2015). Transcriptome dynamics of developing photoreceptors in three-dimensional retina cultures recapitulates temporal sequence of human cone and rod differentiation revealing cell surface markers and gene networks. Stem Cells (Dayton, OH), 33, 3504–3518.  https://doi.org/10.1002/stem.2122 PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kuwahara, A., Ozone, C., Nakano, T., Saito, K., Eiraku, M., & Sasai, Y. (2015). Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nature Communications, 6, 6286.  https://doi.org/10.1038/ncomms7286 PubMedGoogle Scholar
  33. 33.
    Lowe, A., Harris, R., Bhansali, P., Cvekl, A., & Liu, W. (2016). Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces mediate self-formation of a retinal organoid. Stem Cell Reports, 6, 743–756.  https://doi.org/10.1016/j.stemcr.2016.03.011 PubMedPubMedCentralGoogle Scholar
  34. 34.
    Mellough, C. B., Collin, J., Khazim, M., White, K., Sernagor, E., Steel, D. H., et al. (2015). IGF-1 signaling plays an important role in the formation of three-dimensional laminated neural retina and other ocular structures from human embryonic stem cells. Stem Cells (Dayton, OH), 33, 2416–2430.  https://doi.org/10.1002/stem.2023 Google Scholar
  35. 35.
    Reichman, S., Slembrouck, A., Gagliardi, G., Chaffiol, A., Terray, A., Nanteau, C., et al. (2017). Generation of storable retinal organoids and retinal pigmented epithelium from adherent human iPS cells in xeno-free and feeder-free conditions. Stem Cells (Dayton, OH).  https://doi.org/10.1002/stem.2586 PubMedGoogle Scholar
  36. 36.
    Singh, R. K., Mallela, R. K., Cornuet, P. K., Reifler, A. N., Chervenak, A. P., West, M. D., et al. (2015). Characterization of three-dimensional retinal tissue derived from human embryonic stem cells in adherent monolayer cultures. Stem Cells and Development, 24, 2778–2795.  https://doi.org/10.1089/scd.2015.0144 PubMedPubMedCentralGoogle Scholar
  37. 37.
    Volkner, M., Zschatzsch, M., Rostovskaya, M., Overall, R. W., Busskamp, V., Anastassiadis, K., et al. (2016). Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem Cell Reports, 6, 525–538.  https://doi.org/10.1016/j.stemcr.2016.03.001 PubMedPubMedCentralGoogle Scholar
  38. 38.
    Wahlin, K. J., Maruotti, J. A., Sripathi, S. R., Ball, J., Angueyra, J. M., Kim, C., et al. (2017). Photoreceptor outer segment-like structures in long-term 3D retinas from human pluripotent stem cells. Scientific Reports, 7, 766.  https://doi.org/10.1038/s41598-017-00774-9
  39. 39.
    Wiley, L. A., Burnight, E. R., DeLuca, A. P., Anfinson, K. R., Cranston, C. M., Kaalberg, E. E., et al. (2016). cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness. Scientific Reports, 6, 30742.  https://doi.org/10.1038/srep30742
  40. 40.
    Chow, R. L., & Lang, R. A. (2001). Early eye development in vertebrates. Annual Review of Cell and Developmental Biology, 17, 255–296.  https://doi.org/10.1146/annurev.cellbio.17.1.255 PubMedGoogle Scholar
  41. 41.
    Fuhrmann, S. (2010). Eye morphogenesis and patterning of the optic vesicle. Current Topics in Developmental Biology, 93, 61–84.  https://doi.org/10.1016/b978-0-12-385044-7.00003-5 PubMedPubMedCentralGoogle Scholar
  42. 42.
    Kolb, H., Nelson, R., Ahnelt, P., & Cuenca, N. (2001). Cellular organization of the vertebrate retina. Progress in Brain Research, 131, 3–26.PubMedGoogle Scholar
  43. 43.
    Neves, G., & Lagnado, L. (1999). The retina. Current Biology, 9, R674–R677.PubMedGoogle Scholar
  44. 44.
    Dowling, J. E., & Werblin, F. S. (1971). Synaptic organization of the vertebrate retina. Vision Research, 3, 1–15.PubMedGoogle Scholar
  45. 45.
    Reynolds, J., & Lamba, D. A. (2014). Human embryonic stem cell applications for retinal degenerations. Experimental Eye Research, 123, 151–160.  https://doi.org/10.1016/j.exer.2013.07.010 PubMedGoogle Scholar
  46. 46.
    Lamb, T. D., Collin, S. P., & Pugh, E. N. (2007). Evolution of the vertebrate eye: Opsins, photoreceptors, retina and eye cup. Nature Reviews. Neuroscience, 8, 960–976.  https://doi.org/10.1038/nrn2283 PubMedPubMedCentralGoogle Scholar
  47. 47.
    Andreazzoli, M. (2009). Molecular regulation of vertebrate retina cell fate. Birth Defects Research. Part C, Embryo Today, 87, 284–295.  https://doi.org/10.1002/bdrc.20161 PubMedGoogle Scholar
  48. 48.
    Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M., & Ezzeddine, D. (1996). Cell fate determination in the vertebrate retina. Proceedings of the National Academy of Sciences of the United States of America, 93, 589–595.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Livesey, F. J., & Cepko, C. L. (2001). Vertebrate neural cell-fate determination: Lessons from the retina. Nature Reviews. Neuroscience, 2, 109–118.  https://doi.org/10.1038/35053522 PubMedGoogle Scholar
  50. 50.
    Zaghloul, N. A., Yan, B., & Moody, S. A. (2005). Step-wise specification of retinal stem cells during normal embryogenesis. Biology of the Cell, 97, 321–337.  https://doi.org/10.1042/bc20040521 PubMedGoogle Scholar
  51. 51.
    Klimanskaya, I., Hipp, J., Rezai, K. A., West, M., Atala, A., & Lanza, R. (2004). Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning and Stem Cells, 6, 217–245.  https://doi.org/10.1089/clo.2004.6.217 PubMedGoogle Scholar
  52. 52.
    Carr, A. J., Vugler, A., Lawrence, J., Chen, L. L., Ahmado, A., Chen, F. K., et al. (2009). Molecular characterization and functional analysis of phagocytosis by human embryonic stem cell-derived RPE cells using a novel human retinal assay. Molecular Vision, 15, 283–295.  https://doi.org/10.5966/sctm.2012-0163 PubMedPubMedCentralGoogle Scholar
  53. 53.
    Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., et al. (2009). Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell, 5, 396–408.  https://doi.org/10.1016/j.stem.2009.07.002 PubMedGoogle Scholar
  54. 54.
    Buchholz, D. E., Hikita, S. T., Rowland, T. J., Friedrich, A. M., Hinman, C. R., Johnson, L. V., et al. (2009). Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells (Dayton, OH), 27, 2427–2434.  https://doi.org/10.1002/stem.189 Google Scholar
  55. 55.
    Singh, R., Phillips, M. J., Kuai, D., Meyer, J., Markin J. M., Smith, M. A., et al. (2013). Functional analysis of serially expanded human iPS cell-derived RPE cultures. Investigative Ophthalmology & Visual Science, 54, 6767–6778.  https://doi.org/10.1093/hmg/dds469 PubMedPubMedCentralGoogle Scholar
  56. 56.
    Singh, R., Shen, W., Kuai, D., Martin, J. M., Guo, X., Smith, M. A., et al. (2013). iPS cell modeling of best disease: Insights into the pathophysiology of an inherited macular degeneration. Human Molecular Genetics, 22, 593–607.  https://doi.org/10.1016/j.stem.2016.03.021 PubMedPubMedCentralGoogle Scholar
  57. 57.
    Tucker, B. A., Mullins, R. F., Streb, L. M., Anfinson, K., Eyestone, M. E., Kaalberg, E., et al. (2013). Patient-specific iPSC-derived photoreceptor precursor cells as a means to investigate retinitis pigmentosa. eLife, e00824, 2.  https://doi.org/10.1038/mt.2014.100 PubMedPubMedCentralGoogle Scholar
  58. 58.
    Riazifar, H., Jia, Y., Chen, J., Lynch, G., & Huang, T. (2014). Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells. Stem Cells Translational Medicine, 3, 424–432.  https://doi.org/10.5966/sctm.2013-0147 PubMedPubMedCentralGoogle Scholar
  59. 59.
    Ferrer, M., Corneo, B., Davis, J., Wan, Q., Miyagishima, K. J., King, R., et al. (2014). A multiplex high-throughput gene expression assay to simultaneously detect disease and functional markers in induced pluripotent stem cell-derived retinal pigment epithelium. Stem Cells Translational Medicine, 3, 911–922.  https://doi.org/10.1167/iovs.11-9313 Google Scholar
  60. 60.
    Maruotti, J., Sripathi, S. R., Bharti, K., Fuller, J., Wahlin, K. J., Ranganathan, V., et al. (2015). Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America, 112, 10950–10955.  https://doi.org/10.1073/pnas.1422818112 Google Scholar
  61. 61.
    Zhou, S., Flamier, A., Abdouh, M., Tetreault, N., Barabino, A., Wadhwa, S., et al. (2015). Differentiation of human embryonic stem cells into cone photoreceptors through simultaneous inhibition of BMP, TGFbeta and Wnt signaling. Development, 142, 3294–3306.  https://doi.org/10.1242/dev.125385 PubMedGoogle Scholar
  62. 62.
    Sluch, V. M., Davis, C. H., Ranganathan, V., Kerr, J. M., Krick, K., Martin, R., et al. (2015). Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line. Scientific Reports, 5, 16595.  https://doi.org/10.1038/srep16595
  63. 63.
    Ohlemacher, S. K., Sridhar, A., Xiao, Y., Hochstetler, A. E., Sarfarazi, M., Cummins, T. R., et al. (2016). Stepwise differentiation of retinal ganglion cells from human pluripotent stem cells enables analysis of glaucomatous neurodegeneration. Stem Cells (Dayton, OH).  https://doi.org/10.1002/stem.2356 PubMedPubMedCentralGoogle Scholar
  64. 64.
    Barnea-Cramer, A. O., Wang, W., Lu, S. J., Singh, M. S., Luo, C., Huo, H., et al. (2016). Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice. Scientific Reports, 6, 29784.Google Scholar
  65. 65.
    Gill, K. P., Hung, S. S., Sharov, A., Lo, C. Y., Needham, K., Lidgerwood, G. E., et al. (2016). Enriched retinal ganglion cells derived from human embryonic stem cells. Scientific Reports, 6, 30552.  https://doi.org/10.1038/srep30552
  66. 66.
    Sluch, V. M., Chamling, X., Liu, M. M., Berlinicke, C. A., Cheng, J., Mitchell, K. L., et al. (2017). Enhanced stem cell differentiation and immunopurification of genome engineered human retinal ganglion cells. Stem Cells Translational Medicine, 6, 1972–1986.  https://doi.org/10.1002/sctm.17-0059 PubMedGoogle Scholar
  67. 67.
    Langer, K. B., Ohlemacher, S. K., Phillips, M. J., Fligor, C. M., Jiang, P., Gamm, D. M., et al. (2018). Retinal ganglion cell diversity and subtype specification from human pluripotent stem cells. Stem Cell Reports, 10, 1282–1293.  https://doi.org/10.1016/j.stemcr.2018.02.010 PubMedPubMedCentralGoogle Scholar
  68. 68.
    Reh, T. A., Lamba, D., & Gust, J. (2010). Directing human embryonic stem cells to a retinal fate. Methods in Molecular Biology, 636, 139–153.  https://doi.org/10.1007/978-1-60761-691-7_9 PubMedGoogle Scholar
  69. 69.
    Osakada, F., Jin, Z. B., Hirami, Y., Ikeda, H., Danjyo, T., Watanabe, K., et al. (2009). In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. Journal of Cell Science, 122, 3169–3179.  https://doi.org/10.1242/jcs.050393 PubMedGoogle Scholar
  70. 70.
    Bharti, K., Miller, S. S., & Arnheiter, H. (2011). The new paradigm: Retinal pigment epithelium cells generated from embryonic or induced pluripotent stem cells. Pigment Cell & Melanoma Research, 24, 21–34.  https://doi.org/10.1111/j.1755-148X.2010.00772.x Google Scholar
  71. 71.
    Buchholz, D. E., Pennington, B. O., Croze, R. H., Hinman, C. R., Coffey, P. J., & Clegg, D. O. (2013). Rapid and efficient directed differentiation of human pluripotent stem cells into retinal pigmented epithelium. Stem Cells Translational Medicine, 2, 384–393.  https://doi.org/10.1038/nbt.3070 PubMedPubMedCentralGoogle Scholar
  72. 72.
    Capowski, E. E., Simonett, J. M., Clark, E. M., Wright, L. S., Howden S. E., Wallace, K. A., et al. (2014). Loss of MITF expression during human embryonic stem cell differentiation disrupts retinal pigment epithelium development and optic vesicle cell proliferation. Human Molecular Genetics, 23, 6332–6344.  https://doi.org/10.1007/978-1-4614-3209-8_20 Google Scholar
  73. 73.
    Clarke, L., Ballios, B. G., & van der Kooy, D. (2012). Generation and clonal isolation of retinal stem cells from human embryonic stem cells. The European Journal of Neuroscience, 36, 1951–1959.  https://doi.org/10.1111/j.1460-9568.2012.08123.x PubMedGoogle Scholar
  74. 74.
    Maeda, T., Lee, M. J., Palczewska, G., Marsilli, S., Tesar, P. J., Palczewski, K., et al. (2013). Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. The Journal of Biological Chemistry, 288, 34484–34493.  https://doi.org/10.5966/sctm.2014-0038 PubMedPubMedCentralGoogle Scholar
  75. 75.
    Okamoto, S., & Takahashi, M. (2011). Induction of retinal pigment epithelial cells from monkey iPS cells. Investigative Ophthalmology & Visual Science, 52, 8785–8790.  https://doi.org/10.1167/iovs.11-8129 Google Scholar
  76. 76.
    Singh, R., Kuai, D., Guziewicz, K. E., Meyer, J., Wilson M., Lu, J., et al. (2015). Pharmacological modulation of photoreceptor outer segment degradation in a human iPS cell model of inherited macular degeneration. Molecular Therapy, 23, 1700–1711.  https://doi.org/10.1093/hmg/ddu053 PubMedPubMedCentralGoogle Scholar
  77. 77.
    Vugler, A., Carr, A. J., Lawrence, J., Chen, L. L., Burrell, K., Wright A., et al. (2008). Elucidating the phenomenon of HESC-derived RPE: Anatomy of cell genesis, expansion and retinal transplantation. Experimental Neurology, 214, 347–361.  https://doi.org/10.1016/j.expneurol.2008.09.007 Google Scholar
  78. 78.
    Boucherie, C., Sowden, J. C., & Ali, R. R. (2011). Induced pluripotent stem cell technology for generating photoreceptors. Regenerative Medicine, 6, 469–479.  https://doi.org/10.2217/rme.11.37 PubMedPubMedCentralGoogle Scholar
  79. 79.
    Deng, F., Chen, M., Liu, Y., Hu, H., Xiong, Y., Xu, C., et al. (2016). Stage-specific differentiation of iPSCs toward retinal ganglion cell lineage. Molecular Vision, 22, 536–547.Google Scholar
  80. 80.
    Li, K., Zhong, X., Yang, S., Luo, S., Li, K., Liu, Y., et al. (2017). HiPSC-derived retinal ganglion cells grow dendritic arbors and functional axons on a tissue-engineered scaffold. Acta Biomaterialia.  https://doi.org/10.1016/j.actbio.2017.02.032 PubMedGoogle Scholar
  81. 81.
    Tanaka, T., Yokoi, T., Tamalu, F., Watanabe, S., Nishina, S., & Azuma, N. (2015). Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells. Scientific Reports, 5, 8344.  https://doi.org/10.1038/srep08344 PubMedPubMedCentralGoogle Scholar
  82. 82.
    Teotia, P., Chopra, D. A., Dravid, S. M., Van Hook, M. J., Qiu, F., Morrison, J., et al. (2017). Generation of functional human retinal ganglion cells with target specificity from pluripotent stem cells by chemically defined recapitulation of developmental mechanism. Stem Cells (Dayton, OH), 35, 572–585.  https://doi.org/10.1002/stem.2513 PubMedPubMedCentralGoogle Scholar
  83. 83.
    Jin, Z. B., & Takahashi, M. (2012). Generation of retinal cells from pluripotent stem cells. Progress in Brain Research, 201, 171–181.  https://doi.org/10.1016/b978-0-444-59544-7.00008-1 PubMedGoogle Scholar
  84. 84.
    Parfitt, D. A., Lane, A., Ramsden C. M., Carr, A. J., Munro, P. M., Jovanovic, K., et al. (2016). Identification and correction of mechanisms underlying inherited blindness in human iPSC-derived optic cups. Cell Stem Cell, 18, 769–781.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Wiley, L. A., Burnight, E. R., Songstad, A. E., Drack, A. V., Mullins, R. F., Stone, E. M., et al. (2015). Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases. Progress in Retinal and Eye Research, 44, 15–35.  https://doi.org/10.1016/j.preteyeres.2014.10.002 PubMedGoogle Scholar
  86. 86.
    Congdon, N., O'Colmain, B., Klaver, C. C., Klein, R., Muñoz, B., Friedman, D. S., et al. (2004). Causes and prevalence of visual impairment among adults in the United States. Archives of Ophthalmology, 122, 477–485.  https://doi.org/10.1001/archopht.122.4.477
  87. 87.
    Veleri, S., Lazar, C. H., Chang, B., Sieving, P. A., Banin, E., & Swaroop, A. (2015). Biology and therapy of inherited retinal degenerative disease: Insights from mouse models. Disease Models & Mechanisms, 8, 109–129.  https://doi.org/10.1242/dmm.017913 Google Scholar
  88. 88.
    Fletcher, E. L., Jobling, A. I., Greferath, U., Mills, S. A., Waugh M., Ho, T., et al. (2014). Studying age-related macular degeneration using animal models. Optometry and Vision Science, 91, 878–886.  https://doi.org/10.1097/opx.0000000000000322 PubMedPubMedCentralGoogle Scholar
  89. 89.
    Fletcher, E. L., Jobling, A. I., Vessey, K. A., Luu, C., Guymer, R. H., & Baird, P. N. (2011). Animal models of retinal disease. Progress in Molecular Biology and Translational Science, 100, 211–286.  https://doi.org/10.1016/b978-0-12-384878-9.00006-6 PubMedGoogle Scholar
  90. 90.
    Iglesias, A. I., Springelkamp, H., Ramdas, W. D., Klaver, C. C., Willemsen, R., & van Duijn, C. M. (2015). Genes, pathways, and animal models in primary open-angle glaucoma. Eye (London, England), 29, 1285–1298.  https://doi.org/10.1038/eye.2015.160 Google Scholar
  91. 91.
    Jones, M. K., Lu, B., Girman, S., & Wang, S. (2017). Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases. Progress in Retinal and Eye Research.  https://doi.org/10.1016/j.preteyeres.2017.01.004 PubMedPubMedCentralGoogle Scholar
  92. 92.
    Kostic, C., & Arsenijevic, Y. (2016). Animal modelling for inherited central vision loss. The Journal of Pathology, 238, 300–310.  https://doi.org/10.1002/path.4641 Google Scholar
  93. 93.
    Niwa, M., Aoki, H., Hirata, A., Tomita, H., Green, P. G., & Hara, A. (2016). Retinal cell degeneration in animal models. International Journal of Molecular Sciences, 17.  https://doi.org/10.3390/ijms17010110 PubMedCentralGoogle Scholar
  94. 94.
    Pennesi, M. E., Neuringer, M., & Courtney, R. J. (2012). Animal models of age related macular degeneration. Molecular Aspects of Medicine, 33, 487–509.  https://doi.org/10.1016/j.mam.2012.06.003 PubMedPubMedCentralGoogle Scholar
  95. 95.
    Jin, Z. B., Okamoto, S., Osakada, F., Homma, K., Assawachananont, J., Hirami, Y., et al. (2011). Modeling retinal degeneration using patient-specific induced pluripotent stem cells. PLoS One, 6, e17084.  https://doi.org/10.1371/journal.pone.0017084 PubMedPubMedCentralGoogle Scholar
  96. 96.
    Tucker, B. A., Scheetz, T. E., Mullins, R. F., DeLuca, A. P., Hoffmann, J. M., Johnston, R. M., et al. (2011). Exome sequencing and analysis of induced pluripotent stem cells identify the cilia-related gene male germ cell-associated kinase (MAK) as a cause of retinitis pigmentosa. Proceedings of the National Academy of Sciences of the United States of America, 108, E569–E576.  https://doi.org/10.1073/pnas.1108918108 Google Scholar
  97. 97.
    Minegishi, Y., Iejima, D., Kobayashi, H., Chi, Z. L., Kawase, K., Yamamoto T., et al. (2013). Enhanced optineurin E50K-TBK1 interaction evokes protein insolubility and initiates familial primary open-angle glaucoma. Human Molecular Genetics, 22, 3559–3567.  https://doi.org/10.1093/hmg/ddt210 PubMedGoogle Scholar
  98. 98.
    Lustremant, C., Habeler, W., Plancheron, A., Goureau, O., Grenot, L., de la Grange, P., et al. (2013). Human induced pluripotent stem cells as a tool to model a form of Leber congenital amaurosis. Cellular Reprogramming, 15, 233–246.  https://doi.org/10.1089/cell.2012.0076 PubMedGoogle Scholar
  99. 99.
    Tucker, B. A., Solivan-Timpe, F., Roos, B. R., Anfinson, K. R., Robin, A. L., Wiley L. A., et al. (2014). Duplication of TBK1 stimulates autophagy in iPSC-derived retinal cells from a patient with normal tension glaucoma. Journal of Stem Cell Research and Therapy, 3, 161.  https://doi.org/10.4172/2157-7633.1000161
  100. 100.
    Yang, J., Li, Y., Chan, L., Tsai, Y. T., Wu, W. H., Nguyen, H. V., et al. (2014). Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines. Human Molecular Genetics, 23, 3445–3455.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Cereso, N., Pequignot, M. O., Robert, L., Becker, F., De Luca, V., Nabholz, N., et al. (2014). Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient. Molecular Therapy – Methods & Clinical Development, 1, 14011.  https://doi.org/10.1038/mtm.2014.11 Google Scholar
  102. 102.
    Yoshida, T., Ozawa, Y., Suzuki, K., Yuki, K., Ohyama, N., Akamatsu, W., et al. (2014). The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Molecular Brain, 7, 45.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Li, Y., Wu, W. H., Hsu, C. W., Nguyen, H. V., Tsai, Y. T., Chan, L., et al. (2014). Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects. Molecular Therapy, 22, 1688–1697.  https://doi.org/10.1186/1756-6606-7-45 PubMedPubMedCentralGoogle Scholar
  104. 104.
    Schwarz, N., Carr, A. J., Lane, A., Moeller, F., Chen, L. L., Aguilà, M., et al. (2015). Translational read-through of the RP2 Arg120stop mutation in patient iPSC-derived retinal pigment epithelium cells. Human Molecular Genetics, 24, 972–986.  https://doi.org/10.1371/journal.pone.0017084 PubMedPubMedCentralGoogle Scholar
  105. 105.
    Moshfegh, Y., Velez, G., Li, Y., Bassuk, A. G., Mahajan, V. B., & Tsang, S. H. (2016). BESTROPHIN1 mutations cause defective chloride conductance in patient stem cell-derived RPE. Human Molecular Genetics, 25, 2672–2680.  https://doi.org/10.1093/hmg/ddw126 PubMedPubMedCentralGoogle Scholar
  106. 106.
    Chen, J., Riazifar, H., Guan, M. X., & Huang, T. (2016). Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets. Stem Cell Research & Therapy, 7, 2.  https://doi.org/10.1186/s13287-015-0264-1 Google Scholar
  107. 107.
    Saini, J. S., Corneo, B., Miller, J. D., Kiehl, T. R., Qang, Q., Boles, N. C., et al. (2017). Nicotinamide ameliorates disease phenotypes in a human iPSC model of age-related macular degeneration. Cell Stem Cell.  https://doi.org/10.1016/j.stem.2016.12.015 PubMedPubMedCentralGoogle Scholar
  108. 108.
    Ramsden, C. M., Nommiste, B., R Lane, A., Carr, A. F., Powner, M. B., J K Smart, M., et al. (2017). Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs. Scientific Reports, 7, 51.  https://doi.org/10.1038/s41598-017-00142-7
  109. 109.
    Hallam, D., Collin, J., Bojic, S., Chichagova, V., Buskin, A., Xu, Y., et al. (2017). An induced pluripotent stem cell patient specific model of complement factor H (Y402H) polymorphism displays characteristic features of age-related macular degeneration and indicates a beneficial role for UV light exposure. Stem Cells (Dayton, OH), 35, 2305–2320.  https://doi.org/10.1002/stem.2708 PubMedPubMedCentralGoogle Scholar
  110. 110.
    Comyn, O., Lee, E., & MacLaren, R. E. (2010). Induced pluripotent stem cell therapies for retinal disease. Current Opinion in Neurology, 23, 4–9.  https://doi.org/10.1097/WCO.0b013e3283352f96 PubMedPubMedCentralGoogle Scholar
  111. 111.
    Wu, S. M., & Hochedlinger, K. (2011). Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nature Cell Biology, 13, 497–505.  https://doi.org/10.1038/ncb0511-497 PubMedPubMedCentralGoogle Scholar
  112. 112.
    Chichagova, V., Hallam D., Collin, J., Buskin, A., Saretzki, G., Armstrong, L., et al. (2017). Human iPSC disease modelling reveals functional and structural defects in retinal pigment epithelial cells harbouring the m.3243A > G mitochondrial DNA mutation. Scientific Reports, 7, 12320.  https://doi.org/10.1038/s41598-017-12396-2
  113. 113.
    Croze, R. H., & Clegg, D. O. (2014). Differentiation of pluripotent stem cells into retinal pigmented epithelium. Developments in Ophthalmology, 53, 81–96.  https://doi.org/10.1159/000357361 PubMedPubMedCentralGoogle Scholar
  114. 114.
    Du, H., Lim, S. L., Grob, S., & Zhang, K. (2011). Induced pluripotent stem cell therapies for geographic atrophy of age-related macular degeneration. Seminars in Ophthalmology, 26, 216–224.  https://doi.org/10.3109/08820538.2011.577498 PubMedPubMedCentralGoogle Scholar
  115. 115.
    Howden, S. E., Gore, A., Li, Z., Fung, H. L., Nisler, B. S., Nie, J., et al. (2011). Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy. Proceedings of the National Academy of Sciences of the United States of America, 108, 6537–6542.  https://doi.org/10.5966/sctm.2012-0163 PubMedPubMedCentralGoogle Scholar
  116. 116.
    Jin, Z. B., Okamoto, S., Xiang, P., & Takahashi, M. (2012). Integration-free induced pluripotent stem cells derived from retinitis pigmentosa patient for disease modeling. Stem Cells Translational Medicine, 1, 503–509.  https://doi.org/10.2119/molmed.2012.00242 PubMedPubMedCentralGoogle Scholar
  117. 117.
    Leach, L. L., Buchholz, D. E., Nadar, V. P., Lowenstein, S. E., & Clegg, D. O. (2015). Canonical/beta-catenin Wnt pathway activation improves retinal pigmented epithelium derivation from human embryonic stem cells. Investigative Ophthalmology & Visual Science, 56, 1002–1013.  https://doi.org/10.1167/iovs.14-15835 Google Scholar
  118. 118.
    Phillips, M. J., Perez, E. T., Martin, J. M., Reshel S. T., Wallace, K. A., Capowski, E. E., et al. (2014). Modeling human retinal development with patient-specific induced pluripotent stem cells reveals multiple roles for visual system homeobox 2. Stem Cells (Dayton, OH), 32, 1480–1492.  https://doi.org/10.1093/hmg/ddu351 PubMedPubMedCentralGoogle Scholar
  119. 119.
    Yvon, C., Ramsden, C. M., Lane, A., Powner, M. B., da Cruz, L., Coffey, P. J., et al. (2015). Using stem cells to model diseases of the outer retina. Computational and Structural Biotechnology Journal, 13, 382–389.  https://doi.org/10.1016/j.csbj.2015.05.001 PubMedPubMedCentralGoogle Scholar
  120. 120.
    Cedrone, C., Mancino, R., Cerulli, A., Cesareo, M., & Nucci, C. (2008). Epidemiology of primary glaucoma: Prevalence, incidence, and blinding effects. Progress in Brain Research, 173, 3–14.  https://doi.org/10.1016/s0079-6123(08)01101-1 PubMedGoogle Scholar
  121. 121.
    Tham, Y. C., Li, X., Wong, T. Y., Quigley, H. A., Aung, T., & Cheng, C. Y. (2014). Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology, 121, 2081–2090.  https://doi.org/10.1016/j.ophtha.2014.05.013 PubMedGoogle Scholar
  122. 122.
    Maekawa, Y., Onishi, A., Matsushita, K., Koide, N., Mandai, M., Suzuma, K., et al. (2016). Optimized culture system to induce neurite outgrowth from retinal ganglion cells in three-dimensional retinal aggregates differentiated from mouse and human embryonic stem cells. Current Eye Research, 41, 558–568.  https://doi.org/10.3109/02713683.2015.1038359
  123. 123.
    Bershteyn, M., Nowakowski, T. J., Pollen, A. A., Di Lullo, E., Nene, A., Wynshaw-Boris, A., et al. (2017). Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia cell. Stem Cell, 20, 435–449 e434.  https://doi.org/10.1016/j.stem.2016.12.007 Google Scholar
  124. 124.
    Qian, X., Nguyen, H. N., Jacob, F., Song, H., & Ming, G. L. (2017). Using brain organoids to understand Zika virus-induced microcephaly. Development, 144, 952–957.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden S. C., Hammack, C., et al. (2016). Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell, 165, 1238–1254.  https://doi.org/10.1242/dev.140707 PubMedPubMedCentralGoogle Scholar
  126. 126.
    Grskovic, M., Javaherian, A., Strulovici, B., & Daley, G. Q. (2011). Induced pluripotent stem cells—opportunities for disease modelling and drug discovery. Nature Reviews. Drug Discovery, 10, 915–929.  https://doi.org/10.1038/nrd3577 PubMedGoogle Scholar
  127. 127.
    Gunaseeli, I., Doss, M. X., Antzelevitch, C., Hescheler, J., & Sachinidis, A. (2010). Induced pluripotent stem cells as a model for accelerated patient- and disease-specific drug discovery. Current Medicinal Chemistry, 17, 759–766.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Wahlin, K. J., Maruotti, J., & Zack, D. J. (2014). Modeling retinal dystrophies using patient-derived induced pluripotent stem cells. Advances in Experimental Medicine and Biology, 801, 157–164.  https://doi.org/10.1007/978-1-4614-3209-8_20 PubMedPubMedCentralGoogle Scholar
  129. 129.
    Wright, L. S., Phillips, M. J., Pinilla, I., Hei, D., & Gamm, D. M. (2014). Induced pluripotent stem cells as custom therapeutics for retinal repair: Progress and rationale. Experimental Eye Research, 123, 161–172.  https://doi.org/10.1016/j.exer.2013.12.001 PubMedPubMedCentralGoogle Scholar
  130. 130.
    Chang, Y. C., Chang, W. C., Hung, K. H., Yang, D. M., Cheng, Y. H., Liao, Y. W., et al. (2014). The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: Identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress. Frontiers in Aging Neuroscience, 6, 191.  https://doi.org/10.3389/fnagi.2014.00191
  131. 131.
    Kokkinaki, M., Sahibzada, N., & Golestaneh, N. (2011). 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 (Dayton, OH), 29, 825–835.  https://doi.org/10.1002/stem.635 Google Scholar
  132. 132.
    Santos-Ferreira, T. F., Borsch, O., & Ader, M. (2016). Rebuilding the missing part-A review on photoreceptor transplantation. Frontiers in Systems Neuroscience, 10, 105.PubMedGoogle Scholar
  133. 133.
    Streilein, J. W. (2003). Ocular immune privilege: The eye takes a dim but practical view of immunity and inflammation. Journal of Leukocyte Biology, 74, 179–185.  https://doi.org/10.1083/jcb.201006020 PubMedGoogle Scholar
  134. 134.
    Sung, C. H., & Chuang, J. Z. (2010). The cell biology of vision. The Journal of Cell Biology, 190, 953–963.PubMedPubMedCentralGoogle Scholar
  135. 135.
    Lamba, D. A., Gust, J., & Reh, T. A. (2009). Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell, 4, 73–79.  https://doi.org/10.1016/j.stem.2008.10.015 PubMedPubMedCentralGoogle Scholar
  136. 136.
    Zhu, J., Cifuentes, H., Reynolds, J., & Lamba, D. A. (2017). Immunosuppression via loss of IL2rgamma enhances long-term functional integration of hESC-derived photoreceptors in the mouse retina cell. Stem Cell, 20(374–384), e375.  https://doi.org/10.1016/j.stem.2016.11.019 Google Scholar
  137. 137.
    Coles, B. L., Angénieux, B., Inoue, T., Del Rio-Tsonis, K., Spence, J. R., McInnes, R. R., et al. (2004). Facile isolation and the characterization of human retinal stem cells. Proceedings of the National Academy of Sciences of the United States of America, 101, 15772–15777.Google Scholar
  138. 138.
    Czekaj, M., Haas, J., Gebhardt, M., Müller-Reichert, T., Humphries, P., Farrar, J., et al. (2012). In vitro expanded stem cells from the developing retina fail to generate photoreceptors but differentiate into myelinating oligodendrocytes. PLoS One, 7, e41798.PubMedPubMedCentralGoogle Scholar
  139. 139.
    Klassen, H. J., Ng, T. F., Kurimoto, Y., Kirov, I., Shatos, M., Coffey, P., et al. (2004). Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior. Investigative Ophthalmology & Visual Science, 45, 4167–4173.  https://doi.org/10.1167/iovs.04-0511 Google Scholar
  140. 140.
    Eberle, D., Kurth, T., Santos-Ferreira, T., Wilson, J., Corbeil, D., & Ader, M. (2012). Outer segment formation of transplanted photoreceptor precursor cells. PLoS One, 7, e46305.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Lund, R. D., Wang, S., Klimanskaya, I., Holmes, T., Ramos-Kelsey R., Lu, B., et al. (2006). Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning and Stem Cells, 8, 189–199.  https://doi.org/10.1089/clo.2006.8.189 PubMedGoogle Scholar
  142. 142.
    Assawachananont, J., Mandai, M., Okamoto, S., Yamada, C. Eiraku, M., Yonemura, S., et al. (2014). Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports, 2, 662–674.PubMedPubMedCentralGoogle Scholar
  143. 143.
    Chao, J. R., Lamba, D. A., Klesert, T. R., Torre, A., Hoshino, A., Taylor R. J., et al. (2017). Transplantation of human embryonic stem cell-derived retinal cells into the subretinal space of a non-human primate. Translational Vision Science & Technology, 6, 4.  https://doi.org/10.1167/tvst.6.3.4 Google Scholar
  144. 144.
    da Cruz, L., Chen, F. K., Ahmado, A., Greenwood, J., & Coffey, P. (2007). RPE transplantation and its role in retinal disease. Progress in Retinal and Eye Research, 26, 598–635.  https://doi.org/10.1016/j.preteyeres.2007.07.001 PubMedGoogle Scholar
  145. 145.
    Falkner-Radler, C. I., Krebs, I., Glittenberg, C., Povazay, B., Drexler, W., Graf, A., et al. (2011). Human retinal pigment epithelium (RPE) transplantation: Outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study. The British Journal of Ophthalmology, 95, 370–375.  https://doi.org/10.1136/bjo.2009.176305 PubMedGoogle Scholar
  146. 146.
    Kamao, H., Mandai, M., Okamoto, S., Sakai, N., Suga, A., Sugita, S., et al. (2014). Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Reports, 2, 205–218.  https://doi.org/10.5966/sctm.2014-0038 PubMedPubMedCentralGoogle Scholar
  147. 147.
    Lakowski, J., Gonzalez-Cordero, A., West, E. L., Han, Y. T., Welby E., Naeem, A., et al. (2015). Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina. Stem Cells (Dayton, OH), 33, 2469–2482PubMedPubMedCentralGoogle Scholar
  148. 148.
    Mandai, M., Watanabe, A., Kurimoto, Y., Hirami, Y., Morinaga, C., Daimon, T., et al. (2017). Autologous induced stem-cell-derived retinal cells for macular degeneration. The New England Journal of Medicine, 376, 1038–1046.  https://doi.org/10.1056/NEJMoa1608368 PubMedGoogle Scholar
  149. 149.
    Park, U. C., Cho, M. S., Park, J. H., Kim, S. J., Ku, S. Y., Choi, Y. M., et al. (2011). Subretinal transplantation of putative retinal pigment epithelial cells derived from human embryonic stem cells in rat retinal degeneration model. Clinical and Experimental Reproductive Medicine, 38, 216–221.  https://doi.org/10.5653/cerm.2011.38.4.216 PubMedPubMedCentralGoogle Scholar
  150. 150.
    Petrus-Reurer, S., Bartuma, H., Aronsson, M., Westman, S., Lanner, F., & Kvanta, A. (2018). Subretinal transplantation of human embryonic stem cell derived-retinal pigment epithelial cells into a large-eyed model of geographic atrophy. Journal of Visualized Experiments.  https://doi.org/10.3791/56702
  151. 151.
    Radtke, N. D., Aramant, R. B., Petry, H. M., Green, P. T., Pidwell, D. J., & Seiler, M. J. (2008). Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium. American Journal of Ophthalmology, 146, 172–182.  https://doi.org/10.1016/j.ajo.2008.04.009 PubMedGoogle Scholar
  152. 152.
    Schwartz, S. D., Regillo, C. D., Lam, B. L., Eliott, D., Rosenfeld, P. J., Gregori, N. Z., et al. (2015). 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, 385, 509–516.  https://doi.org/10.1016/S0140-6736(14)61376-3 Google Scholar
  153. 153.
    Cooke, J. A., & Meyer, J. S. (2015). Human pluripotent stem cell-derived retinal ganglion cells: Applications for the study and treatment of optic neuropathies. Current Ophthalmology Reports, 3, 200–206.PubMedPubMedCentralGoogle Scholar
  154. 154.
    Lebrun-Julien, F., & Di Polo, A. (2008). Molecular and cell-based approaches for neuroprotection in glaucoma. Optometry and Vision Science, 85, 417–424.  https://doi.org/10.1097/OPX.0b013e31817841f7 PubMedGoogle Scholar
  155. 155.
    Sluch, V. M., & Zack, D. J. (2014). Stem cells, retinal ganglion cells and glaucoma. Developments in Ophthalmology, 53, 111–121.PubMedPubMedCentralGoogle Scholar
  156. 156.
    Shirai, H., Mandai, M., Matsushita, K., Kuwahara, A., Yonemura, S., Nakano, T., et al. (2016). Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration. Proceedings of the National Academy of Sciences of the United States of America, 113, E81–E90.Google Scholar
  157. 157.
    Boucherie, C., Mukherjee, S., Henckaerts, E., Thrasher, A. J., Sowden, J. C., & Ali, R. R. (2013). Brief report: Self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors. Stem Cells (Dayton, OH), 31, 408–414.  https://doi.org/10.1002/stem.1268 Google Scholar
  158. 158.
    Viczian, A. S., Solessio, E. C., Lyou, Y., & Zuber, M. E. (2009). Generation of functional eyes from pluripotent cells. PLoS Biology, 7, e1000174.  https://doi.org/10.1371/journal.pbio.1000174 PubMedPubMedCentralGoogle Scholar
  159. 159.
    Lu, B., Malcuit, C., Wang, S., Girman, S., Francis, P., Lemieux, L., et al. (2009). Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration. Stem Cells (Dayton, OH), 27, 2126–2135.  https://doi.org/10.1002/stem.149
  160. 160.
    MacLaren, R. E., Pearson, R. A., MacNeil, A., Douglas, R. H., Salt, T. E., Akimoto, M., et al. (2006). Retinal repair by transplantation of photoreceptor precursors. Nature, 444, 203–207.  https://doi.org/10.1038/nature05161 Google Scholar
  161. 161.
    Song, W. K., Park, K. M., Kim, H. J., Lee, J. H., Choi, J., Chong, S. Y., et al. (2015). Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: Preliminary results in Asian patients. Stem Cell Reports, 4, 860–872.  https://doi.org/10.1038/srep12910
  162. 162.
    Rowland, T. J., Blaschke, A. J., Buchholz, D. E., Hikita, S. T., Johnson, L. V., & Clegg, D. O. (2013). Differentiation of human pluripotent stem cells to retinal pigmented epithelium in defined conditions using purified extracellular matrix proteins. Journal of Tissue Engineering and Regenerative Medicine, 7, 642–653.  https://doi.org/10.1002/term.1458 PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Akshayalakshmi Sridhar
    • 1
  • Kirstin B. Langer
    • 1
  • Clarisse M. Fligor
    • 1
  • Matthew Steinhart
    • 2
  • Casey A. Miller
    • 1
  • Kimberly T. Ho-A-Lim
    • 1
  • Sarah K. Ohlemacher
    • 1
  • Jason S. Meyer
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of BiologyIndiana University Purdue University IndianapolisIndianapolisUSA
  2. 2.Medical Science Training ProgramIndiana UniversityBloomingtonUSA
  3. 3.Department of Medical and Molecular GeneticsIndiana UniversityIndianapolisUSA
  4. 4.Stark Neurosciences Research InstituteIndiana UniversityIndianapolisUSA

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