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
Part of the Fundamental Biomedical Technologies book series (FBMT)


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.


Human pluripotent stem cells Retina Organoids Development Disease 


  1. 1.
    Barnstable, C. J. (1987). A molecular view of vertebrate retinal development. Molecular Neurobiology, 1, 9–46.PubMedCrossRefGoogle 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.CrossRefPubMedGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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. PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Pearson, R. A. (2014). Advances in repairing the degenerate retina by rod photoreceptor transplantation. Biotechnology Advances, 32, 485–491. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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). PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. CrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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.
  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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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). PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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.
  40. 40.
    Chow, R. L., & Lang, R. A. (2001). Early eye development in vertebrates. Annual Review of Cell and Developmental Biology, 17, 255–296. PubMedCrossRefGoogle Scholar
  41. 41.
    Fuhrmann, S. (2010). Eye morphogenesis and patterning of the optic vesicle. Current Topics in Developmental Biology, 93, 61–84. PubMedPubMedCentralCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Neves, G., & Lagnado, L. (1999). The retina. Current Biology, 9, R674–R677.PubMedCrossRefGoogle Scholar
  44. 44.
    Dowling, J. E., & Werblin, F. S. (1971). Synaptic organization of the vertebrate retina. Vision Research, 3, 1–15.PubMedCrossRefGoogle Scholar
  45. 45.
    Reynolds, J., & Lamba, D. A. (2014). Human embryonic stem cell applications for retinal degenerations. Experimental Eye Research, 123, 151–160. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Andreazzoli, M. (2009). Molecular regulation of vertebrate retina cell fate. Birth Defects Research. Part C, Embryo Today, 87, 284–295. PubMedCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. CrossRefGoogle 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. PubMedCrossRefGoogle 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.
  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). PubMedPubMedCentralCrossRefGoogle 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.
  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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Jin, Z. B., & Takahashi, M. (2012). Generation of retinal cells from pluripotent stem cells. Progress in Brain Research, 201, 171–181. PubMedCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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.
  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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Kostic, C., & Arsenijevic, Y. (2016). Animal modelling for inherited central vision loss. The Journal of Pathology, 238, 300–310. CrossRefPubMedGoogle 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. PubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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.
  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.PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  113. 113.
    Croze, R. H., & Clegg, D. O. (2014). Differentiation of pluripotent stem cells into retinal pigmented epithelium. Developments in Ophthalmology, 53, 81–96. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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.
  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. CrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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. CrossRefGoogle 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. PubMedCrossRefGoogle Scholar
  134. 134.
    Sung, C. H., & Chuang, J. Z. (2010). The cell biology of vision. The Journal of Cell Biology, 190, 953–963.PubMedPubMedCentralCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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.CrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. CrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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, 2469–2482PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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. PubMedCrossRefGoogle 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. CrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle 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. PubMedCrossRefGoogle Scholar
  155. 155.
    Sluch, V. M., & Zack, D. J. (2014). Stem cells, retinal ganglion cells and glaucoma. Developments in Ophthalmology, 53, 111–121.PubMedPubMedCentralCrossRefGoogle 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.CrossRefGoogle 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. CrossRefGoogle 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. PubMedPubMedCentralCrossRefGoogle 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.
  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. PubMedCrossRefGoogle 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.
  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. PubMedCrossRefGoogle 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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