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Lab generated retina: Realizing the dream

Published online by Cambridge University Press:  22 May 2014

CARLA B. MELLOUGH ,
JOSEPH COLLIN ,
EVELYNE SERNAGOR ,
NICHOLAS K. WRIDE ,
DAVID H.W. STEEL  and
MAJLINDA LAKO
CARLA B. MELLOUGH
Affiliation:
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
JOSEPH COLLIN
Affiliation:
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
EVELYNE SERNAGOR
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom
NICHOLAS K. WRIDE
Affiliation:
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom Sunderland Eye Infirmary, Sunderland, United Kingdom
DAVID H.W. STEEL
Affiliation:
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom Sunderland Eye Infirmary, Sunderland, United Kingdom
MAJLINDA LAKO*
Affiliation:
Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
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Abstract

Blindness represents an increasing global problem with significant social and economic impact upon affected patients and society as a whole. In Europe, approximately one in 30 individuals experience sight loss and 75% of those are unemployed, a social burden which is very likely to increase as the population of Europe ages. Diseases affecting the retina account for approximately 26% of blindness globally and 70% of blindness in the United Kingdom. To date, there are no treatments to restore lost retinal cells and improve visual function, highlighting an urgent need for new therapeutic approaches. A pioneering breakthrough has demonstrated the ability to generate synthetic retina from pluripotent stem cells under laboratory conditions, a finding with immense relevance for basic research, in vitro disease modeling, drug discovery, and cell replacement therapies. This review summarizes the current achievements in pluripotent stem cell differentiation toward retinal cells and highlights the steps that need to be completed in order to generate human synthetic retinae with high efficiency and reproducibly from patient-specific pluripotent stem cells.

Keywords

Neural retinaRetinal pigmented epitheliumHuman pluripotent stem cellsDifferentiationAge related macular degeneration (AMD)Hereditary retinal dystrophies (HRDs)
Type
Review Articles
Information
Visual Neuroscience , Volume 31 , Issue 4-5: Strategies for Restoring Sight in Retinal Dystrophies , September 2014 , pp. 317 - 332
Copyright
Copyright © Cambridge University Press 2014 

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References

Abdel-Meguid, A., Lappas, A., Hartmann, K., Auer, F., Schrage, N., Thumann, G., & Kirchhof, B. (2003). One year follow up of macular translocation with 360 degree retinotomy in patients with age related macular degeneration. The British Journal of Ophthalmology 87, 615–621.CrossRefGoogle ScholarPubMed
Aisenbrey, S., Lafaut, B.A., Szurman, P., Grisanti, S., Lüke, C., Krott, R., Thumann, G., Fricke, J., Neugebauer, A.,Hilgers, R.D., Esser, P., Walter, P. & Bartz-Schmidt, K.U. (2002). Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration. Archives Ophthalmology 120, 451–459.Google Scholar
Aisenbrey, S., Lafaut, B.A., Szurman, P., Hilgers, R.D., Esser, P., Walter, P., Bartz-Schmidt, K.U. & Thumann, G. (2006). Iris pigment epithelial translocation in the treatment of exudative macular degeneration: A 3-year follow-up. Archives Ophthalmology 124, 183–188.CrossRefGoogle ScholarPubMed
Algvere, P.V., Gouras, P. & Dafgård Kopp, E. (1999). Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. European Journal of Ophthalmology 9, 217–230.Google Scholar
Aoki, H., Hara, A., Niwa, M., Yamada, Y. & Kunisada, T. (2009). In vitro and in vivo differentiation of human embryonic stem cells into retina-like organs and comparison with that from mouse pluripotent epiblast stem cells. Developmental Dynamics 238, 2266–2279.Google Scholar
Arias, L. (2010). Treatment of retinal pigment epithelial detachment with antiangiogenic therapy. Clinical Ophthalmology 4, 369–374.CrossRefGoogle ScholarPubMed
Bae, D., Mondragon-Teran, P., Hernandez, D., Ruban, L., Mason, C., Bhattacharya, S.S. & Veraitch, F.S. (2012). Hypoxia enhances the generation of retinal progenitor cells from human induced pluripotent and embryonic stem cells. Stem Cells and Development 21(8), 1344–1355.Google Scholar
Bainbridge, J.W., Smith, A.J., Barker, S.S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G.E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S.S., Thrasher, A.J., Fitzke, F.W., Carter, B.J., Rubin, G.S., Moore, A.T. & Ali, R.R. (2008). Effect of gene therapy on visual function in Leber’s congenital amaurosis. The New England Journal of Medicine 358:2231–2239.Google Scholar
Barber, A.C., Hippert, C. & Duran, Y. (2013). Repair of the degenerate retina by photoreceptor transplantation. Proceedings of the National Academy of Science 110, 354–359.CrossRefGoogle ScholarPubMed
Binder, S., Krebs, I., Hilgers, R.D., Abri, A., Stolba, U., Assadoulina, A., Kellner, L., Stanzel, B.V., Jahn, C. & Feichtinger, H. (2004). Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: A prospective trial. Investigative Ophthalmology & Visual Science 45, 4151–4160.Google Scholar
Birch, D.G., Weleber, R.G., Duncan, J.L., Jaffe, G.J. & Tao, W. (2013). Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa. American Journal of Ophthalmology 156, 283–292.CrossRefGoogle ScholarPubMed
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 31, 408–414.Google Scholar
Buchholz, D.E., Hikita, S.T., Rowland, T.J., Friedrich, A.M., Hinman, C.R., Johnson, L.V. & Clegg, D.O. (2009). Derivation of functional retinal pigmented epithelium from induced pluripotent stem cells. Stem Cells 27, 2427–2434.CrossRefGoogle ScholarPubMed
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.Google Scholar
Carr, A.J., Vugler, A.A., Hikita, S.T., Lawrence, J.M., Gias, C., Chen, L.L., Buchholz, D.E., Ahmado, A., Semo, M., Smart, M.J., Hasan, S., da Cruz, L., Johnson, L.V., Clegg, D.O. & Coffey, P.J. (2009). Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 4, e8152.CrossRefGoogle ScholarPubMed
Catalani, E., Tomassini, S., Dal Monte, M., Bosco, L. & Casini, G. (2009). Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and FGFR2 in postnatal mouse retina. Cell Tissue Research 336, 423–438.Google Scholar
Chen, F.K., Uppal, G.S., MacLaren, R.E., Coffey, P.J., Rubin, G.S., Tufail, A., Aylward, G.W. & Da Cruz, L. (2009). Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration. Clinical & Experimental Ophthalmology 37, 275–285.CrossRefGoogle ScholarPubMed
Cideciyan, A.V., Jacobson, S.G., Beltran, W.A., Sumaroka, A., Swider, M., Iwabe, S., Roman, A.J., Olivares, M.B., Schwartz, S.B., Komáromy, A.M., Hauswirth, W.W. & Aguirre, G.D. (2013). Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proceedings of the National Academy of Sciences of the United States of America 110, E517–E525.Google Scholar
Collin, J. & Lako, M. (2011). Concise review: Putting a finger on stem cell biology: Zinc finger nuclease-driven targeted genetic editing in human pluripotent stem cells. Stem Cells 29(7), 1021–1033.Google Scholar
Coppola, D., Ouban, A. & Gilbert-Barness, E. (2009). Expression of the insulin-like growth factor receptor 1 during human embryogenesis. Fetal and Pediatric Pathology 28, 47–54.CrossRefGoogle ScholarPubMed
Davis, A.A., Matzuk, M.M. & Reh, T.A. (2000). Activin A promotes progenitor differentiation into photoreceptors in rodent retina. Molecular and Cellular Neurosciences 15, 11–21.CrossRefGoogle ScholarPubMed
Eckardt, C., Eckardt, U. & Conrad, H.G. (1999). Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration. Graefes Archive for Clinical and Experimental Ophthalmology 237, 313–325.Google Scholar
Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T. & Sasai, Y. (2011). Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472, 51–56.Google Scholar
Falkner-Radler, C.I., Krebs, I., Glittenberg, C., Povazay, B., Drexler, W., Graf, A. & Binder, S. (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.CrossRefGoogle Scholar
Fischer, B. & Bavister, B.D. (1993). Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. Journal of Reproduction and Fertility 99, 673–679.CrossRefGoogle ScholarPubMed
Forristal, C.E., Wright, K.L., Hanley, N.A., Oreffo, R.O. & Houghton, F.D. (2010). Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction 139, 85–97. doi: 10.1530/REP-09-0300.Google Scholar
Garita-Hernández, M., Diaz-Corrales, F., Lukovic, D., González-Guede, I., Diez-Lloret, A., Valdés-Sánchez, M.L., Massalini, S., Erceg, S. & Bhattacharya, S.S. (2013). Hypoxia increases the yield of photoreceptors differentiating from mouse embryonic stem cells and improves the modeling of retinogenesis in vitro. Stem Cells 31, 966–978.CrossRefGoogle ScholarPubMed
Georges-Labouesse, E., Mark, M., Messaddeq, N. & Gansmüller, A. (1998). Essential role of alpha 6 integrins in cortical and retinal lamination. Current Biology 8, 983–986.Google Scholar
Gerecht, S., Burdick, J.A., Ferreira, L.S., Townsend, S.A., Langer, R. & Vunjak-Novakovic, G. (2007). Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 104, 11298–11303.Google Scholar
Gong, J., Sagiv, O., Cai, H., Tsang, S.H. & Del Priore, L.V. (2008). Effects of extracellular matrix and neighboring cells on induction of human embryonic stem cells into retinal or retinal pigment epithelial progenitors. Experimental Eye Research 86, 957–965.CrossRefGoogle ScholarPubMed
Gonzalez-Cordero, A., West, E.L., Pearson, R.A., Duran, Y., Carvalho, L.S., Chu, C.J., Naeem, A., Blackford, S.J., Georgiadis, A., Lakowski, J., Hubank, M., Smith, A.J., Bainbridge, J.W., Sowden, J.C. & Ali, R.R. (2013). Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nature Biotechnology 31, 741–747.CrossRefGoogle ScholarPubMed
Grimm, C., Wenzel, A., Groszer, M., Mayser, H., Seeliger, M., Samardzija, M., Bauer, C., Gassmann, M. & Remé, C.E. (2002). HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nature Medicine 8, 718–724.Google Scholar
Haider, N.B., Jacobson, S.G., Cideciyan, A.V., Swiderski, R., Streb, L.M., Searby, C., Beck, G., Hockey, R., Hanna, D.B., Gorman, S., Duhl, D., Carmi, R., Bennett, J., Weleber, R.G., Fishman, G.A., Wright, A.F., Stone, E.M. & Sheffield, V.C. (2000). Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nature Genetics 24, 127–131.Google Scholar
Haruta, M., Kosaka, M. & Kaneagye, Y. (2001). Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue. Nature Neuroscience 4, 1163–1164.Google Scholar
Hirami, Y., Osakada, F., Takahashi, K., Okita, K., Yamanaka, S., Ikeda, H., Yoshimura, N. & Takahashi, M. (2009). Generation of retinal cells from mouse and human induced pluripotent stem cells. Neuroscience Letters 458, 126–131.CrossRefGoogle ScholarPubMed
Hollyfield, J.G. (1999). Hyaluronan and the functional organization of the interphotoreceptor matrix. Investigative Ophthalmology & Visual Science 40, 2767–2769.Google Scholar
Hunter, D.D., Murphy, M.D., Olsson, C.V. & Brunken, W.J. (1992). S-laminin expression in adult and developing retinae: A potential cue for photoreceptor morphogenesis. Neuron 8, 399–413.Google Scholar
Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., Cohen, M.A., Even-Ram, S., Berman-Zaken, Y., Matzrafi, L., Rechavi, G., Banin, E. & Reubinoff, B. (2009). Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5, 396–408.Google Scholar
Jin, Z.B., Okamoto, S., Osakada, F., Homma, K., Assawachananont, J., Hirami, Y., Iwata, T. & Takahashi, M. (2011). Modeling retinal degeneration using patient-specific induced pluripotent stem cells. PloS one 6(2), e17084.Google Scholar
Kaiser, P.K., Brown, D.M., Zhang, K., Hudson, H.L., Holz, F.G., Shapiro, H., Schneider, S. & Acharya, N.R. (2007). Ranibizumab for predominantly classic neovascular age-related macular degeneration: Subgroup analysis of first-year Anchor results. American Journal of Ophthalmology 144, 850–857.Google Scholar
Kazanis, I., Lathia, J.D., Vadakkan, T.J., Raborn, E., Wan, R., Mughal, M.R., Eckley, D.M., Sasaki, T., Patton, B., Mattson, M.P., Hirschi, K.K., Dickinson, M.E. & ffrench-Constant, C. (2010). Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals. The Journal of Neuroscience 30, 9771–9781.Google Scholar
Keenan, T.D., Clark, S.J., Unwin, R.D., Ridge, L.A., Day, A.J. & Bishop, P.N. (2012). Mapping the differential distribution of proteoglycan core proteins in the adult human retina, choroid, and sclera. Investigative Ophthalmology & Visual Science 53(12), 7528–7538.Google Scholar
Kelley, M.W., Turner, J.K. & Reh, T.A. (1994). Retinoic acid promotes differentiation of photoreceptors in vitro. Development 120, 2091–2102.Google Scholar
Keung, A.J., Asuri, P., Kumar, S. & Schaffer, D.V. (2012). Soft microenvironments promote the early neurogenic differentiation but not self-renewal of human pluripotent stem cells. Integrative Biology (Cambridge) 4, 1049–1058.CrossRefGoogle Scholar
Keung, A.J., de Juan-Pardo, E.M., Schaffer, D.V. & Kumar, S. (2011). Rho GTPases mediate the mechanosensitive lineage commitment of neural stem cells. Stem Cells 29, 1886–1897.CrossRefGoogle ScholarPubMed
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 Stem Cells 6, 217–245.CrossRefGoogle ScholarPubMed
Krishnadev, N., Meleth, A.D. & Chew, E.Y. (2010). Nutritional supplements for age-related macular degeneration. Current Opinion in Ophthalmology 21, 184–189.CrossRefGoogle ScholarPubMed
Kubo, F., Takeichi, M. & Nakagawa, S. (2003). Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130, 587–598.Google Scholar
Lako, M., Armstrong, L. & Stojkovic, M. (2010). Induced pluripotent stem cells: It looks simple but can looks deceive?. Stem Cells 28, 845–850.Google Scholar
Lakowski, J., Baron, M., Bainbridge, J., Barber, A.C., Pearson, R.A., Ali, R.R. & Sowden, J.C. (2010). Cone and rod photoreceptor transplantation in models of the childhood retinopathy Leber congenital amaurosis using flow-sorted Crx-positive donor cells. Human Molecular Genetics 19(23), 4545–4559.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Lancaster, M.A., Renner, M., Martin, C.A., Wenzel, D., Bicknell, L.S., Hurles, M.E., Homfray, T., Penninger, J.M., Jackson, A.P. & Knoblich, J.A. (2013). Cerebral organoids model human brain development and microcephaly. Nature. 501, 373–379.CrossRefGoogle ScholarPubMed
Li, X., Ma, W., Zhuo, Y., Yan, R.T. & Wang, S.Z. (2010). Using neurogenin to reprogram chick RPE to produce photoreceptor like neurons. Investigative Ophthalmology & Visual Science 51, 516–525.Google Scholar
Li, Y., Tsai, Y.T., Hsu, C.W., Erol, D., Yang, J., Wu, W.H., Davis, R.J., Egli, D. & Tsang, S.H. (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.Google Scholar
Libby, R.T., Champliaud, M.F., Claudepierre, T., Xu, Y., Gibbons, E.P., Koch, M., Burgeson, R.E., Hunter, D.D. & Brunken, W.J. (2000). Laminin expression in adult and developing retinae: Evidence of two novel CNS laminins. The Journal of Neuroscience 20, 6517–6528.Google Scholar
Libby, R.T., Lavallee, C.R., Balkema, G.W., Brunken, W.J. & Hunter, D.D. (1999). Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS. The Journal of Neuroscience 19(17), 9399–9411.Google Scholar
Lombardini, J.B. (1991). Taurine: Retinal function. Brain Research Brain Research Reviews 16, 151–169.Google Scholar
Lund, R.D., Wang, S., Klimanskaya, I., Holmes, T., Ramos-Kelsey, R., Lu, B., Girman, S., Bischoff, N., Sauvé, Y. & Lanza, R. (2006). Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning and Stem Cells 8(3), 189–199.Google Scholar
MacLaren, R.E., Bird, A.C., Sathia, P.J. & Aylward, G.W. (2005). Long-term results of submacular surgery combined with macular translocation of the retinal pigment epithelium in neovascular age-related macular degeneration. Ophthalmology 112, 2081–2087.Google Scholar
MacLaren, R.E., Pearson, R.A., MacNeil, A., Douglas, R.H., Salt, T.E., Akimoto, M., Swaroop, A., Sowden, J.C. & Ali, R.R. (2006). Retinal repair by transplantation of photoreceptor precursors. Nature 444, 203–207.Google Scholar
MacLaren, R.E., Uppal, G.S., Balaggan, K.S., Tufail, A., Munro, P.M., Milliken, A.B., Ali, R.R., Rubin, G.S., Aylward, G.W. & da Cruz, L. (2007). Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration. Ophthalmology 114, 561–570.Google Scholar
MacNeil, A., Pearson, R.A., McLaren, R.E., Smith, A.J., Sowden, J.C. & Ali, R.R. (2007). Comparative analysis of progenitor cells isolated from the iris, pars plana and ciliary body of the adult porcine eye. Stem Cells 25, 2430–2438.Google Scholar
Maguire, A.M., Simonelli, F., Pierce, E.A., Pugh, E.N. Jr., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K.A., Testa, F., Surace, E.M., Rossi, S., Lyubarsky, A., Arruda, V.R., Konkle, B., Stone, E., Sun, J., Jacobs, J., Dell’Osso, L., Hertle, R., Ma, J.X., Redmond, T.M., Zhu, X., Hauck, B., Zelenaia, O., Shindler, K.S., Maguire, M.G., Wright, J.F., Volpe, N.J., McDonnell, J.W., Auricchio, A., High, K.A. & Bennett, J. (2008). Safety and efficacy of gene transfer for Leber’s congenital amaurosis. The New England Journal of Medicine 358, 2240–2248.CrossRefGoogle ScholarPubMed
Maslim, J., Valter, K., Egensperger, R., Holländer, H. & Stone, J. (1997). Tissue oxygen during a critical developmental period controls the death and survival of photoreceptors. Investigative Ophthalmology & Visual Science 38, 1667–1677.Google Scholar
Mellough, C.B., Sernagor, E., Moreno-Gimeno, I., Steel, D.H. & Lako, M. (2012). Efficient stage-specific differentiation of human pluripotent stem cells toward retinal photoreceptor cells. Stem Cells 30, 673–686.Google Scholar
Mellough, C.B., Steel, D.H. & Lako, M. (2009). Genetic basis of inherited macular dystrophies and implications for stem cell therapy. Stem Cells 27, 2833–2845.Google Scholar
Mervin, K. & Stone, J. (2002). Regulation by oxygen of photoreceptor death in the developing and adult C57BL/6J mouse. Experimental Eye Research 75, 715–722.Google Scholar
Meyer, J.S., Howden, S.E., Wallace, K.A., Verhoeven, A.D., Wright, L.S., Capowski, E.E., Pinilla, I., Martin, J.M., Tian, S., Stewart, R., Pattnaik, B., Thomson, J.A. & Gamm, D.M. (2011). Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells 29, 1206–1218.Google Scholar
Meyer, J.S., Shearer, R.L., Capowski, E.E., Wright, L.S., Wallace, K.A., McMillan, E.L., Zhang, S.C. & Gamm, D.M. (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.Google Scholar
Mizeracka, K., DeMaso, C.R. & Cepko, C.L. (2013). Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate. Development 140, 3188–3197.CrossRefGoogle ScholarPubMed
Mondragon-Teran, P., Baboo, J.Z., Mason, C., Lye, G.J. & Veraitch, F.S. (2011 a). The full spectrum of physiological oxygen tensions and step-changes in oxygen tension affects the neural differentiation of mouse embryonic stem cells. Biotechnology Progress 27, 1700–1708.Google Scholar
Mondragon-Teran, P., Baboo, J.Z., Mason, C., Lye, G.J. & Veraitch, F.S. (2011 b). The full spectrum of physiological oxygen tensions and step-changes in oxygen tension affects the neural differentiation of mouse embryonic stem cells. Biotechnology Progress 27, 1700–1708. doi: 10.1002/btpr.675. Epub 2011 Sep 7.CrossRefGoogle ScholarPubMed
Mruthyunjaya, P., Stinnett, S.S. & Toth, C.A. (2004). Change in visual function after macular translocation with 360 degrees retinectomy for neovascular age-related macular degeneration. Ophthalmology 111, 1715–1724.Google Scholar
Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., Saito, K., Yonemura, S., Eiraku, M. & Sasai, Y. (2012). Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10, 771–785.Google Scholar
Nistor, G., Seiler, M.J., Yan, F., Ferguson, D. & Keirstead, H.S. (2010). Three-dimensional early retinal progenitor 3D tissue constructs derived from human embryonic stem cells. Journal of Neuroscience Methods 190, 63–70.CrossRefGoogle ScholarPubMed
Osakada, F., Ikeda, H., Mandai, M., Wataya, T., Watanabe, K., Yoshimura, N., Akaike, A., Sasai, Y. & Takahashi, M. (2008). Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nature Biotechnology 26, 215–224.CrossRefGoogle ScholarPubMed
Otani, A., Dorrell, M.I., Kinder, K., Moreno, S.K., Nusinowitz, S., Banin, E., Heckenlively, J. & Friedlander, M. (2004). Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. The Journal of Clinical Investigation 114, 765–774.CrossRefGoogle ScholarPubMed
Pascolini, D. & Mariotti, S.P. (2012). Global estimates of visual impairment: 2010. The British Journal of Ophthalmology 96(5), 614–618.CrossRefGoogle ScholarPubMed
Patel, A. & McFarlane, S. (2000). Overexpression of FGF-2 alters cell fate specification in the developing retina of Xenopus laevis. Developmental Biology 222, 170–180.Google Scholar
Pera, E.M., Wessely, O., Li, S.Y. & De Robertis, E.M. (2001). Neural and head induction by insulin-like growth factor signals. Developmental Cell 1, 655–665.Google Scholar
Pertile, G. & Claes, C. (2002). Macular translocation with 360 degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization. American Journal of Ophthalmology 134, 560–565.Google Scholar
Phillips, M.J., Wallace, K.A., Dickerson, S.J., Miller, M.J., Verhoeven, A.D., Martin, J.M., Wright, L.S., Shen, W., Capowski, E.E., Percin, E.F., Perez, E.T., Zhong, X., Canto-Soler, M.V. & Gamm, D.M. (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.Google Scholar
Pinzón-Duarte, G., Daly, G., Li, Y.N., Koch, M. & Brunken, W.J. (2010). Defective formation of the inner limiting membrane in laminin beta2- and gamma3-null mice produces retinal dysplasia. Investigative Ophthalmology & Visual Science 51, 1773–1782.Google Scholar
Pittack, C., Grunwald, G.B. & Reh, T.A. (1997). Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos. Development 124, 805–816.Google Scholar
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.Google Scholar
Rashid, S.T. & Vallier, L. (2010). Induced pluripotent stem cells–alchemist’s tale or clinical reality?. Expert Reviews in Molecular Medicine 12, 25.Google Scholar
Riesenberg, A.N., Liu, Z., Kopan, R. & Brown, N.L. (2009). Rbpj cell autonomous regulation of retinal ganglion cell and cone photoreceptor fates in the mouse retina. The Journal of Neuroscience 29, 12865–12877.Google Scholar
http://www.riken.jp/en/pr/press/2013/20130730_1/ (accessed 11/10/13).Google Scholar
Rodesch, F., Simon, P., Donner, C. & Jauniaux, E. (1992). Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstetrics and Gynecology 80, 283–285.Google Scholar
Rodriguez-de la Rosa, L., Fernandez-Sanchez, L., Germain, F., Murillo-Cuesta, S., Varela-Nieto, I., de la Villa, P. & Cuenca, N. (2012). Age-related functional and structural retinal modifications in the Igf1-/- null mouse. Neurobiology of Disease 46, 476–485.Google Scholar
Rosenfeld, P.J., Brown, D.M., Heier, J.S., Boyer, D.S., Kaiser, P.K., Chung, C.Y., Kim, R.Y. & MARINA Study Group (2006). Ranibizumab for neovascular age-related macular degeneration. The New England Journal of Medicine 355, 1419–1431.Google Scholar
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.Google Scholar
Sakuta, H., Suzuki, R., Takahashi, H., Kato, A., Shintani, T., Iemura, S.I., Yamamoto, T.S., Ueno, N. & Noda, M. (2001). Ventroptin: A BMP-4 antagonist expressed in a double-gradient pattern in the retina. Science 293, 111–115.Google Scholar
Schwartz, S.D., Hubschman, J.P., Heilwell, G., Franco-Cardenas, V., Pan, C.K., Ostrick, R.M., Mickunas, E., Gay, R., Klimanskaya, I. & Lanza, R. (2012). Embryonic stem cell trials for macular degeneration: A preliminary report. Lancet 379, 713–720.Google Scholar
Singh, R., Shen, W., Kuai, D., Martin, J.M., Guo, X., Smith, M.A., Perez, E.T., Phillips, M.J., Simonett, J.M., Wallace, K.A., Verhoeven, A.D., Capowski, E.E., Zhang, X., Yin, Y., Halbach, P.J., Fishman, G.A., Wright, L.S., Pattnaik, B.R. & Gamm, D.M. (2013). iPS cell modeling of best disease: insights into the pathophysiology of an inherited macular degeneration. Human Molecular Genetics 22, 593–607.Google Scholar
Smith, A.J., Bainbridge, J.W. & Ali, R.R. (2009). Prospects for retinal gene replacement therapy. Trends in Genetics 25, 156–165.Google Scholar
Stenkamp, D.L. & Frey, R.A. (2003). Extraretinal and retinal hedgehog signaling sequentially regulate retinal differentiation in zebrafish. Developmental Biology 258, 349–363.Google Scholar
Sundaram, V., Moore, A.T., Ali, R.R. & Bainbridge, J.W.(2012). Retinal dystrophies and gene therapy. European Journal of Pediatrics 171, 757–765.CrossRefGoogle ScholarPubMed
Swaroop, A., Kim, D. & Forrest, D. (2010). Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nature Reviews Neuroscience 11, 563–576.Google Scholar
Taylor, C.J., Bolton, E.M., Pocock, S., Sharples, L.D., Pedersen, R.A. & Bradley, J.A. (2005). Banking on human embryonic stem cells: Estimating the number of donor cell lines needed for HLA matching. Lancet 366, 2019–2025.Google Scholar
Tezel, T.H., Del Priore, L.V., Berger, A.S. & Kaplan, H.J. (2007). Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. American Journal of Ophthalmology 143, 584–595.Google Scholar
Tucker, B.A., Scheetz, T.E., Mullins, R.F., DeLuca, A.P., Hoffmann, J.M., Johnston, R.M., Jacobson, S.G., Sheffield, V.C. & Stone, E.M. (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 Science United States of America 108, E569–E576.Google Scholar
Vaajasaari, H., Ilmarinen, T., Juuti-Uusitalo, K., Rajala, K., Onnela, N., Narkilahti, S., Suuronen, R., Hyttinen, J., Uusitalo, H. & Skottman, H. (2011). Toward the defined and xeno-free differentiation of functional human pluripotent stem cell-derived retinal pigment epithelial cells. Molecular Vision 17, 558–575.Google Scholar
van Zeeburg, E.J., Maaijwee, K.J., Missotten, T.O., Heimann, H. & van Meurs, J.C. (2012). A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: Results up to 7 years. American Journal of Ophthalmology 153, 120–127.Google Scholar
Vogel-Höpker, A., Momose, T., Rohrer, H., Yasuda, K., Ishihara, L. & Rapaport, D.H. (2000). Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development. Mechanisms of Development 94, 25–36.Google Scholar
Vugler, A., Carr, A.J., Lawrence, J., Chen, L.L., Burrell, K., Wright, A., Lundh, P., Semo, M., Ahmado, A., Gias, C., da Cruz, L., Moore, H., Andrews, P., Walsh, J. & Coffey, P. (2008). Elucidating the phenomenon of HESC-derived RPE: Anatomy of cell genesis, expansion and retinal transplantation. Experimental Neurology 214, 347–361.Google Scholar
West, E.L., Pearson, R.A., Duran, Y., Gonzalez-Cordero, A., MacLaren, R.E., Smith, A.J., Sowden, J.C. & Ali, R.R. (2012). Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival. Cell Transplantation 21, 871–887. doi: 10.3727/096368911X623871. Epub 2012 Feb 2.Google Scholar
Wong, D., Stanga, P., Briggs, M., Lenfestey, P., Lancaster, E., Li, K.K., Lim, K.S. & Groenewald, C. (2004). Case selection in macular relocation surgery for age related macular degeneration. The British Journal of Ophthalmology 88, 186–190.Google Scholar
Wright, L.S., Phillips, M.J., Pinnilla, I., Hei, D. & Gamm, D. (2014). Induced pluripotent stem cells as custom theraupeutics for retinal repair: Progress and rationale. Experimental Eye Research pii: S0014-4835(13)00345-X.Google Scholar
Yamada, Y., Miyamura, N., Suzuma, K. & Kitaoka, T. (2010). Long-term follow-up of full macular translocation for choroidal neovascularization. American Journal of Ophthalmology 149, 453–457.Google Scholar
Yi, X., Schubert, M., Peachey, N.S., Suzuma, K., Burks, D.J., Kushner, J.A., Suzuma, I., Cahill, C., Flint, C.L., Dow, M.A., Leshan, R.L., King, G.L. & White, M.F. (2005). Insulin receptor substrate 2 is essential for maturation and survival of photoreceptor cells. The Journal of Neuroscience 25, 1240–1248.Google Scholar
Zhao, X., Das, A.V. & Bhattacharya, S. (2008). Derivation of neurones with functional properties from adult limbal epithelium: Implications in autologous cell therapy for photoreceptor degeneration. Stem Cells 26, 939–949.Google Scholar
Zhao, S., Hung, F.C., Colvin, J.S., White, A., Dai, W., Lovicu, F.J., Ornitz, D.M. & Overbeek, P.A. (2001). Patterning the optic neuroepithelium by FGF signaling and Ras activation. Development 128, 5051–5060.Google Scholar
Zheng, M.H., Shi, M., Pei, Z., Gao, F., Han, H. & Ding, Y.Q. (2009). The transcription factor RBP-J is essential for retinal cell differentiation and lamination. Molecular Brain 2, 38. doi: 10.1186/1756-6606-2-38.Google Scholar