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Photoreceptor replacement therapy: Challenges presented by the diseased recipient retinal environment

Published online by Cambridge University Press:  19 June 2014

RACHAEL A. PEARSON*
Affiliation:
Department of Genetics, University College London Institute of Ophthalmology, London, UK
CLAIRE HIPPERT
Affiliation:
Department of Genetics, University College London Institute of Ophthalmology, London, UK
ANNA B. GRACA
Affiliation:
Department of Genetics, University College London Institute of Ophthalmology, London, UK
AMANDA C. BARBER
Affiliation:
John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK

Abstract

Vision loss caused by the death of photoreceptors is the leading cause of irreversible blindness in the developed world. Rapid advances in stem cell biology and techniques in cell transplantation have made photoreceptor replacement by transplantation a very plausible therapeutic strategy. These advances include the demonstration of restoration of vision following photoreceptor transplantation and the generation of transplantable populations of donor cells from stem cells. In this review, we present a brief overview of the recent progress in photoreceptor transplantation. We then consider in more detail some of the challenges presented by the degenerating retinal environment that must play host to these transplanted cells, how these may influence transplanted photoreceptor cell integration and survival, and some of the progress in developing strategies to circumnavigate these issues.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2014 

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References

Akimoto, M., Cheng, H., Zhu, D., Brzezinski, J.A., Khanna, R., Filippova, E., Oh, E.C., Jing, Y., Linares, J.L., Brooks, M., Zareparsi, S., Mears, A.J., Hero, A., Glaser, T. & Swaroop, A. (2006). Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proceedings of the National Academy of Sciences of the United States of America 103(10), 38903895.Google Scholar
Anderson, D.H., Guerin, C.J., Erickson, P.A., Stern, W.H. & Fisher, S.K. (1986). Morphological recovery in the reattached retina. Investigative Ophthalmology & Visual Science 27, 168183.Google Scholar
Asher, R.A., Morgenstern, D.A., Fidler, P.S., Adcock, K.H., Oohira, A., Braistead, J.E., Levine, J.M., Margolis, R.U., Rogers, J.H. & Fawcett, J.W. (2000). Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. The Journal of Neuroscience 20, 24272438.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, 22312239.Google Scholar
Bandtlow, C.E. & Schwab, M.E. (2000). NI-35/250/nogo-a: A neurite growth inhibitor restricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS. Glia 29, 175181.Google Scholar
Barber, A.C., Hippert, C., Duran, Y., West, E.L., Bainbridge, J.W., Warre-Cornish, K., Luhmann, U.F., Lakowski, J., Sowden, J.C., Ali, R.R. & Pearson, R.A. (2013). Repair of the degenerate retina by photoreceptor transplantation. Proceedings of the National Academy of Sciences of the United States of America 110, 354359.Google Scholar
Bartsch, U., Oriyakhel, W., Kenna, P.F., Linke, S., Richard, G., Petrowitz, B., Humphries, P., Farrar, G.J. & Ader, M. (2008). Retinal cells integrate into the outer nuclear layer and differentiate into mature photoreceptors after subretinal transplantation into adult mice. Experimental Eye Research 86, 691700.Google Scholar
Bradbury, E.J., Moon, L.D., Popat, R.J., King, V.R., Bennett, G.S., Patel, P.N., Fawcett, J.W. & McMahon, S.B. (2002). Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416, 636640.Google Scholar
Calame, M., Cachafeiro, M., Philippe, S., Schouwey, K., Tekaya, M., Wanner, D., Sarkis, C., Kostic, C. & Arsenijevic, Y. (2011). Retinal degeneration progression changes lentiviral vector cell targeting in the retina. PloS One 6, e23782.Google Scholar
Campbell, M., Humphries, M., Kennan, A., Kenna, P., Humphries, P. & Brankin, B. (2006). Aberrant retinal tight junction and adherens junction protein expression in an animal model of autosomal dominant retinitis pigmentosa: The Rho(-/-) mouse. Experimental Eye Research 83, 484492.Google Scholar
Chen, L.F., FitzGibbon, T., He, J.R. & Yin, Z.Q. (2012). Localization and developmental expression patterns of CSPG-cs56 (aggrecan) in normal and dystrophic retinas in two rat strains. Experimental Neurology 234, 488498.Google Scholar
Cicero, S.A., Johnson, D., Reyntjens, S., Frase, S., Connell, S., Chow, L.M., Baker, S.J., Sorrentino, B.P. & Dyer, M.A. (2009). Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 106, 66856690.Google Scholar
Clark, S.J., Bishop, P.N. & Day, A.J. (2010 a). Complement factor H and age-related macular degeneration: The role of glycosaminoglycan recognition in disease pathology. Biochemical Society Transactions 38, 13421348.Google Scholar
Clark, S.J., Perveen, R., Hakobyan, S., Morgan, B.P., Sim, R.B., Bishop, P.N. & Day, A.J. (2010 b). Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch's membrane in human retina. The Journal of Biological Chemistry 285, 3019230202.Google Scholar
Crespo, D., Asher, R.A., Lin, R., Rhodes, K.E. & Fawcett, J.W. (2007). How does chondroitinase promote functional recovery in the damaged CNS? Experimental Neurology 206, 159171.Google Scholar
Dick, A.D. (2012). Road to fulfilment: Taming the immune response to restore vision. Ophthalmic Research 48, 4349.Google Scholar
Drukker, M., Katz, G., Urbach, A., Schuldiner, M., Markel, G., Itskovitz-Eldor, J., Reubinoff, B., Mandelboim, O. & Benvenisty, N. (2002). Characterization of the expression of MHC proteins in human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America 99, 98649869.Google Scholar
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.Google Scholar
Eberle, D., Schubert, S., Postel, K., Corbeil, D. & Ader, M. (2011). Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina. Investigative Ophthalmology & Visual Science 52, 64626471.Google Scholar
Eiraku, M. & Sasai, Y. (2012). Mouse embryonic stem cell culture for generation of three-dimensional retinal and cortical tissues. Nature Protocols 7, 6979.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, 5156.Google Scholar
Eng, L.F. & Ghirnikar, R.S. (1994). GFAP and astrogliosis. Brain Pathology 4, 229237.Google Scholar
Fawcett, J. (2009). Molecular control of brain plasticity and repair. Progress in Brain Research 175, 501509.Google Scholar
Felix, N.J., Suri, A., Salter-Cid, L., Nadler, S.G., Gujrathi, S., Corbo, M. & Aranda, R. (2010). Targeting lymphocyte co-stimulation: from bench to bedside. Autoimmunity 43, 514525.Google Scholar
Fisher, S.K. & Lewis, G.P. (2003). Muller cell and neuronal remodeling in retinal detachment and reattachment and their potential consequences for visual recovery: A review and reconsideration of recent data. Vision Research 43, 887897.Google Scholar
Fishman, R.S. (1997). Gordon Holmes, the cortical retina, and the wounds of war. The seventh Charles B. Snyder Lecture. Documenta Ophthalmologica. Advances in Ophthalmology 93, 928.Google Scholar
Friedlander, D.R., Milev, P., Karthikeyan, L., Margolis, R.K., Margolis, R.U. & Grumet, M. (1994). The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. The Journal of Cell Biology 125, 669680.Google Scholar
Ghosh, F., Juliusson, B., Arner, K. & Ehinger, B. (1999). Partial and full-thickness neuroretinal transplants. Experimental Eye Research 68, 6774.Google Scholar
Ghosh, F., Larsson, J. & Wilke, K. (2000). MHC expression in fragment and full-thickness allogeneic embryonic retinal transplants. Graefe's Archive for Clinical and Experimental Ophthalmology 238, 589598.Google Scholar
Ghosh, F., Rauer, O. & Arner, K. (2008). Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination. Neuroscience 152, 526533.Google Scholar
Ghosh, F., Wong, F., Johansson, K., Bruun, A. & Petters, R.M. (2004). Transplantation of full-thickness retina in the rhodopsin transgenic pig. Retina 24, 98109.Google Scholar
Gilbert, R.J., McKeon, R.J., Darr, A., Calabro, A., Hascall, V.C. & Bellamkonda, R.V. (2005). CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Molecular and Cellular Neurosciences 29, 545558.Google Scholar
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, 741747.Google Scholar
Grüter, O., Kostic, C., Crippa, S.V., Perez, M.T., Zografos, L., Schorderet, D.F., Munier, F.L. & Arsenijevic, Y. (2005). Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier. Gene Therapy 12(11), 942947.Google Scholar
Gualdoni, S., Baron, M., Lakowski, J., Decembrini, S., Smith, A.J., Pearson, R.A., Ali, R.R. & Sowden, J.C. (2010). Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells 28, 10481059.Google Scholar
Gumy, L.F., Tan, C.L. & Fawcett, J.W. (2010). The role of local protein synthesis and degradation in axon regeneration. Experimental Neurology 223, 2837.Google Scholar
Gust, J. & Reh, T.A. (2011). Adult donor rod photoreceptors integrate into the mature mouse retina. Investigative Ophthalmology & Visual Science 52, 52665272.Google Scholar
Hageman, G.S., Marmor, M.F., Yao, X.Y. & Johnson, L.V. (1995). The interphotoreceptor matrix mediates primate retinal adhesion. Archives of Ophthalmology 113, 655660.Google Scholar
He, Z. & Koprivica, V. (2004). The Nogo signaling pathway for regeneration block. Annual Review of Neuroscience 27, 341368.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, 126131.Google Scholar
Hori, J., Ng, T.F., Shatos, M., Klassen, H., Streilein, J.W. & Young, M.J. (2003). Neural progenitor cells lack immunogenicity and resist destruction as allografts. Stem Cells 21, 405416.Google Scholar
Hughes, E.H., Schlichtenbrede, F.C., Murphy, C.C., Sarra, G.M., Luthert, P.J., Ali, R.R. & Dick, A.D. (2003). Generation of activated sialoadhesin-positive microglia during retinal degeneration. Investigative Ophthalmology & Visual Science 44, 22292234.Google Scholar
Ichijo, H. (2004). Proteoglycans as cues for axonal guidance in formation of retinotectal or retinocollicular projections. Molecular Neurobiology 30, 2333.Google Scholar
Ikeda, H., Osakada, F., Watanabe, K., Mizuseki, K., Haraguchi, T., Miyoshi, H., Kamiya, D., Honda, Y., Sasai, N., Yoshimura, N., Takahashi, M. & Sasai, Y. (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, 1133111336.Google Scholar
Inatani, M., Honjo, M., Otori, Y., Oohira, A., Kido, N., Tano, Y., Honda, Y. & Tanihara, H. (2001). Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Investigative Ophthalmology & Visual Science 42, 19301938.Google Scholar
Inatani, M. & Tanihara, H. (2002). Proteoglycans in retina. Progress in Retinal and Eye Research 21, 429447.Google Scholar
Inatani, M., Tanihara, H., Oohira, A., Honjo, M., Kido, N. & Honda, Y. (2000). Upregulated expression of neurocan, a nervous tissue specific proteoglycan, in transient retinal ischemia. Investigative Ophthalmology & Visual Science 41, 27482754.Google Scholar
Jacobson, S.G., Cideciyan, A.V., Ratnakaram, R., Heon, E., Schwartz, S.B., Roman, A.J., Peden, M.C., Aleman, T.S., Boye, S.L., Sumaroka, A., Conlon, T.J., Calcedo, R., Pang, J.J., Erger, K.E., Olivares, M.B., Mullins, C.L., Swider, M., Kaushal, S., Feuer, W.J., Iannaccone, A., Fishman, G.A., Stone, E.M., Byrne, B.J. & Hauswirth, W.W. (2012). Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: Safety and efficacy in 15 children and adults followed up to 3 years. Archives of Ophthalmology 130, 924.Google Scholar
Jiang, C., Klassen, H., Zhang, X. & Young, M. (2010). Laser injury promotes migration and integration of retinal progenitor cells into host retina. Molecular Vision 16, 983990.Google Scholar
Jiang, H.R., Hwenda, L., Makinen, K., Oetke, C., Crocker, P.R. & Forrester, J.V. (2006). Sialoadhesin promotes the inflammatory response in experimental autoimmune uveoretinitis. Journal of Immunology 177, 22582264.Google Scholar
Jiang, H.R., Lumsden, L. & Forrester, J.V. (1999). Macrophages and dendritic cells in IRBP-induced experimental autoimmune uveoretinitis in B10RIII mice. Investigative Ophthalmology & Visual Science 40, 31773185.Google Scholar
Jiang, L.Q., Jorquera, M. & Streilein, J.W. (1993). Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Investigative Ophthalmology & Visual Science 34, 33473354.Google Scholar
Jiang, L.Q., Jorquera, M., Streilein, J.W. & Ishioka, M. (1995). Unconventional rejection of neural retinal allografts implanted into the immunologically privileged site of the eye. Transplantation 59, 12011207.Google Scholar
Jiang, L.Q. & Streilein, J.W. (1991). Immune responses elicited by transplantation and tissue-restricted antigens expressed on retinal tissues implanted subconjunctivally. Transplantation 52, 513519.Google Scholar
Jones, B.W. & Marc, R.E. (2005). Retinal remodeling during retinal degeneration. Experimental Eye Research 81, 123137.Google Scholar
Jones, B.W., Watt, C.B., Frederick, J.M., Baehr, W., Chen, C.K., Levine, E.M., Milam, A.H., Lavail, M.M. & Marc, R.E. (2003). Retinal remodeling triggered by photoreceptor degenerations. The Journal of Comparative Neurology 464, 116.Google Scholar
Jones, D.G. & Redpath, C.M. (1998). Regeneration in the central nervous system: Pharmacological intervention, xenotransplantation, and stem cell transplantation. Clinical Anatomy 11, 263270.Google Scholar
Kaneko, S., Wang, J., Kaneko, M., Yiu, G., Hurrell, J.M., Chitnis, T., Khoury, S.J. & He, Z. (2006). Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. The Journal of Neuroscience 26, 97949804.Google Scholar
Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger, R.J. & Kolodkin, A.L. (2004). Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44, 961975.Google Scholar
Karlsen, R.L. (1978). The toxic effect of sodium glutamate and DL-alpha-aminoadipic acid on rat retina: Changes in high affinity uptake of putative transmitters. Journal of Neurochemistry 31, 10551061.Google Scholar
Kinouchi, R., Takeda, M., Yang, L., Wilhelmsson, U., Lundkvist, A., Pekny, M. & Chen, D.F. (2003). Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nature Neuroscience 6, 863868.Google Scholar
Klassen, H., Warfvinge, K., Schwartz, P.H., Kiilgaard, J.F., Shamie, N., Jiang, C., Samuel, M., Scherfig, E., Prather, R.S. & Young, M.J. (2008). Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the retina of allorecipients. Cloning and Stem Cells 10, 391402.Google Scholar
Kurimoto, Y., Shibuki, H., Kaneko, Y., Ichikawa, M., Kurokawa, T., Takahashi, M. & Yoshimura, N. (2001). Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia. Neuroscience Letters 306, 5760.Google Scholar
Kwan, A.S., Wang, S. & Lund, R.D. (1999). Photoreceptor layer reconstruction in a rodent model of retinal degeneration. Experimental Neurology 159, 2133.Google Scholar
Lakowski, J., Han, Y.T., Pearson, R.A., Gonzalez-Cordero, A., West, E.L., Gualdoni, S., Barber, A.C., Hubank, M., Ali, R.R. & Sowden, J.C. (2011). Effective transplantation of photoreceptor precursor cells selected via cell surface antigen expression. Stem Cells 29, 13911404.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, 1276912774.Google Scholar
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
Larsen, P.H., Wells, J.E., Stallcup, W.B., Opdenakker, G. & Yong, V.W. (2003). Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 23, 1112711135.Google Scholar
Lee, E.S., Yu, S.H., Jang, Y.J., Hwang, D.Y. & Jeon, C.J. (2011). Transplantation of bone marrow-derived mesenchymal stem cells into the developing mouse eye. Acta Histochemica et Cytochemica 44, 213221.Google Scholar
Lee, H., McKeon, R.J. & Bellamkonda, R.V. (2010). Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proceedings of the National Academy of Sciences of the United States of America 107, 33403345.Google Scholar
Lemons, M.L., Sandy, J.D., Anderson, D.K. & Howland, D.R. (2003). Intact aggrecan and chondroitin sulfate-depleted aggrecan core glycoprotein inhibit axon growth in the adult rat spinal cord. Experimental Neurology 184, 981990.Google Scholar
Lewis, G.P. & Fisher, S.K. (2000). Muller cell outgrowth after retinal detachment: Association with cone photoreceptors. Investigative Ophthalmology & Visual Science 41, 15421545.Google Scholar
Lewis, G.P. & Fisher, S.K. (2003). Up-regulation of glial fibrillary acidic protein in response to retinal injury: Its potential role in glial remodeling and a comparison to vimentin expression. International Review of Cytology 230, 263290.Google Scholar
Li, H., Leung, T.C., Hoffman, S., Balsamo, J. & Lilien, J. (2000). Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan. The Journal of Cell Biology 149, 12751288.Google Scholar
Ma, J., Kabiel, M., Tucker, B.A., Ge, J. & Young, M.J. (2011). Combining chondroitinase ABC and growth factors promotes the integration of murine retinal progenitor cells transplanted into Rho(-/-) mice. Molecular Vision 17, 17591770.Google Scholar
Ma, N. & Streilein, J.W. (1998). Contribution of microglia as passenger leukocytes to the fate of intraocular neuronal retinal grafts. Investigative Ophthalmology & Visual Science 39, 23842393.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, 203207.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, 22402248.Google Scholar
McGee, A.W. & Strittmatter, S.M. (2003). The Nogo-66 receptor: Focusing myelin inhibition of axon regeneration. Trends in Neurosciences 26, 193198.Google Scholar
Mehalow, A.K., Kameya, S., Smith, R.S., Hawes, N.L., Denegre, J.M., Young, J.A., Bechtold, L., Haider, N.B., Tepass, U., Heckenlively, J.R., Chang, B., Naggert, J.K. & Nishina, P.M. (2003). CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Human Molecular Genetics 12, 21792189.Google Scholar
Mellough, C.B., Cui, Q. & Harvey, A.R. (2007). Treatment of adult neural progenitor cells prior to transplantation affects graft survival and integration in a neonatal and adult rat model of selective retinal ganglion cell depletion. Restorative Neurology and Neuroscience 25, 177190.Google Scholar
Meuleman, J., van de Pavert, S.A. & Wijnholds, J. (2004). Crumbs homologue 1 in polarity and blindness. Biochemical Society Transactions 32, 828830.Google Scholar
Meyer, J.S., Katz, M.L., Maruniak, J.A. & Kirk, M.D. (2006). Embryonic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptors. Stem Cells 24, 274283.Google Scholar
Minassian, D.C., Reidy, A., Lightstone, A. & Desai, P. (2011). Modelling the prevalence of age-related macular degeneration (2010-2020) in the UK: Expected impact of anti-vascular endothelial growth factor (VEGF) therapy. The British Journal of Ophthalmology 95, 14331436.Google Scholar
Monje, M.L., Toda, H. & Palmer, T.D. (2003). Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 17601765.Google Scholar
Nakazawa, T., Matsubara, A., Noda, K., Hisatomi, T., She, H., Skondra, D., Miyahara, S., Sobrin, L., Thomas, K.L., Chen, D.F., Grosskreutz, C.L., Hafezi-Moghadam, A. & Miller, J.W. (2006). Characterization of cytokine responses to retinal detachment in rats. Molecular Vision 12, 867878.Google Scholar
Narayanan, K. & Wadhwa, S. (1998). Photoreceptor morphogenesis in the human retina: a scanning electron microscopic study. The Anatomical Record 252(1), 133139.Google Scholar
Nishida, A., Takahashi, M., Tanihara, H., Nakano, I., Takahashi, J.B., Mizoguchi, A., Ide, C. & Honda, Y. (2000). Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Investigative Ophthalmology & Visual Science 41, 42684274.Google Scholar
Olney, J.W. (1968). An electron microscopic study of synapse formation, receptor outer segment development, and other aspects of developing mouse retina. Investigative Ophthalmology 7(3), 250268.Google Scholar
Osakada, F., Ikeda, H., Sasai, Y. & Takahashi, M. (2009). Stepwise differentiation of pluripotent stem cells into retinal cells. Nature Protocols 4, 811824.Google Scholar
Owen, C.G., Jarrar, Z., Wormald, R., Cook, D.G., Fletcher, A.E. & Rudnicka, A.R. (2012). The estimated prevalence and incidence of late stage age related macular degeneration in the UK. The British Journal of Ophthalmology 96, 752756.Google Scholar
Parks, W.C., Wilson, C.L. & Lopez-Boado, Y.S. (2004). Matrix metalloproteinases as modulators of inflammation and innate immunity. Nature Reviews Immunology 4, 617629.Google Scholar
Pasterkamp, R.J. & Verhaagen, J. (2006). Semaphorins in axon regeneration: developmental guidance molecules gone wrong? Philosophical Transactions of the Royal Society of London Series B, Biological Sciences 361, 14991511.Google Scholar
Pearson, R.A. (2014). Advances in repairing the degenerate retina by rod photoreceptor transplantation. Biotechnology Advances 32, 485491.Google Scholar
Pearson, R.A., Barber, A.C., Rizzi, M., Hippert, C., Xue, T., West, E.L., Duran, Y., Smith, A.J., Chuang, J.Z., Azam, S.A., Luhmann, U.F., Benucci, A., Sung, C.H., Bainbridge, J.W., Carandini, M., Yau, K.W., Sowden, J.C. & Ali, R.R. (2012). Restoration of vision after transplantation of photoreceptors. Nature 485, 99103.Google Scholar
Pearson, R.A., Barber, A.C., West, E.L., MacLaren, R.E., Duran, Y., Bainbridge, J.W., Sowden, J.C. & Ali, R.R. (2010). Targeted disruption of outer limiting membrane junctional proteins (Crb1 and ZO-1) increases integration of transplanted photoreceptor precursors into the adult wild-type and degenerating retina. Cell Transplantation 19, 487503.Google Scholar
Pizzi, M.A. & Crowe, M.J. (2007). Matrix metalloproteinases and proteoglycans in axonal regeneration. Experimental Neurology 204, 496511.Google Scholar
Qiu, G., Seiler, M.J., Mui, C., Arai, S., Aramant, R.B., de Juan, E. Jr. & Sadda, S. (2005). Photoreceptor differentiation and integration of retinal progenitor cells transplanted into transgenic rats. Experimental Eye Research 80, 515525.Google Scholar
Ridet, J.L., Malhotra, S.K., Privat, A. & Gage, F.H. (1997). Reactive astrocytes: Cellular and molecular cues to biological function. Trends in Neurosciences 20, 570577.Google Scholar
Roesch, K., Stadler, M.B. & Cepko, C.L. (2012). Gene expression changes within Muller glial cells in retinitis pigmentosa. Molecular Vision 18, 11971214.Google Scholar
Rong, Z., Wang, M., Hu, Z., Stradner, M., Zhu, S., Kong, H., Yi, H., Goldrath, A., Yang, Y.G., Xu, Y. & Fu, X. (2014). An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell 14, 121130.Google Scholar
Roque, R.S., Imperial, C.J. & Caldwell, R.B. (1996). Microglial cells invade the outer retina as photoreceptors degenerate in Royal College of Surgeons rats. Investigative Ophthalmology & Visual Science 37, 196203.Google Scholar
Sakaguchi, D.S., Van Hoffelen, S.J., Grozdanic, S.D., Kwon, Y.H., Kardon, R.H. & Young, M.J. (2005). Neural progenitor cell transplants into the developing and mature central nervous system. Annals of the New York Academy of Sciences 1049, 118134.Google Scholar
Sakaguchi, D.S., Van Hoffelen, S.J., Theusch, E., Parker, E., Orasky, J., Harper, M.M., Benediktsson, A. & Young, M.J. (2004). Transplantation of neural progenitor cells into the developing retina of the Brazilian opossum: An in vivo system for studying stem/progenitor cell plasticity. Developmental Neuroscience 26, 336345.Google Scholar
Sakaguchi, D.S., Van Hoffelen, S.J. & Young, M.J. (2003). Differentiation and morphological integration of neural progenitor cells transplanted into the developing mammalian eye. Annals of the New York Academy of Sciences 995, 127139.Google Scholar
Sam, T.N., Xiao, J., Roehrich, H., Low, W.C. & Gregerson, D.S. (2006). Engrafted neural progenitor cells express a tissue-restricted reporter gene associated with differentiated retinal photoreceptor cells. Cell Transplantation 15, 147160.Google Scholar
Sancho-Pelluz, J., Wunderlich, K.A., Rauch, U., Romero, F.J., van Veen, T., Limb, G.A., Crocker, P.R. & Perez, M.T. (2008). Sialoadhesin expression in intact degenerating retinas and following transplantation. Investigative Ophthalmology & Visual Science 49, 56025610.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, 713720.Google Scholar
Seiler, M.J., Thomas, B.B., Chen, Z., Wu, R., Sadda, S.R. & Aramant, R.B. (2008). Retinal transplants restore visual responses: Trans-synaptic tracing from visually responsive sites labels transplant neurons. The European Journal of Neuroscience 28, 208220.Google Scholar
Singh, M.S., Issa, P.C., Butler, R., Martin, C., Lipinski, D.M., Sekaran, S., Barnard, A.R., Maclaren, R.E. (2013). Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation. Proceedings of the National Academy of Sciences of the United States of America 110, 11011106.Google Scholar
Singhal, S., Lawrence, J.M., Bhatia, B., Ellis, J.S., Kwan, A.S., Macneil, A., Luthert, P.J., Fawcett, J.W., Perez, M.T., Khaw, P.T. & Limb, G.A. (2008). Chondroitin sulfate proteoglycans and microglia prevent migration and integration of grafted Muller stem cells into degenerating retina. Stem Cells 26, 10741082.Google Scholar
Sourisseau, T., Georgiadis, A., Tsapara, A., Ali, R.R., Pestell, R., Matter, K. & Balda, M.S. (2006). Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Molecular and Cellular Biology 26, 23872398.Google Scholar
Streilein, J.W., Ma, N., Wenkel, H., Ng, T.F. & Zamiri, P. (2002). Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Research 42, 487495.Google Scholar
Suzuki, T., Akimoto, M., Imai, H., Ueda, Y., Mandai, M., Yoshimura, N., Swaroop, A. & Takahashi, M. (2007). Chondroitinase ABC treatment enhances synaptogenesis between transplant and host neurons in model of retinal degeneration. Cell Transplantation 16, 493503.Google Scholar
Suzuki, T., Mandai, M., Akimoto, M., Yoshimura, N. & Takahashi, M. (2006). The simultaneous treatment of MMP-2 stimulants in retinal transplantation enhances grafted cell migration into the host retina. Stem Cells 24, 24062411.Google Scholar
Theocharis, A.D., Skandalis, S.S., Tzanakakis, G.N. & Karamanos, N.K. (2010). Proteoglycans in health and disease: Novel roles for proteoglycans in malignancy and their pharmacological targeting. The FEBS Journal 277, 39043923.Google Scholar
Tucker, B., Klassen, H., Yang, L., Chen, D.F. & Young, M.J. (2008). Elevated MMP expression in the MRL mouse retina creates a permissive environment for retinal regeneration. Investigative Ophthalmology & Visual Science 49, 16861695.Google Scholar
Turner, J.E., Seiler, M., Aramant, R. & Blair, J.R. (1988). Embryonic retinal grafts transplanted into the lesioned adult rat retina. Progress in Brain Research 78, 131139.Google Scholar
Tuttle, R., Braisted, J.E., Richards, L.J. & O'Leary, D.D. (1998). Retinal axon guidance by region-specific cues in diencephalon. Development 125, 791801.Google Scholar
Uga, S. & Smelser, G.K. (1973). Electron microscopic study of the development of retinal Mullerian cells. Investigative Ophthalmology 12, 295307.Google Scholar
van de Pavert, S.A., Meuleman, J., Malysheva, A., Aartsen, W.M., Versteeg, I., Tonagel, F., Kamphuis, W., McCabe, C.J., Seeliger, M.W. & Wijnholds, J. (2007). A single amino acid substitution (Cys249Trp) in Crb1 causes retinal degeneration and deregulates expression of pituitary tumor transforming gene Pttg1. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 27, 564573.Google Scholar
Verardo, M.R., Lewis, G.P., Takeda, M., Linberg, K.A., Byun, J., Luna, G., Wilhelmsson, U., Pekny, M., Chen, D.F. & Fisher, S.K. (2008). Abnormal reactivity of Muller cells after retinal detachment in mice deficient in GFAP and vimentin. Investigative Ophthalmology & Visual Science 49, 36593665.Google Scholar
Wang, L., Zhang, Z.G., Zhang, R.L., Gregg, S.R., Hozeska-Solgot, A., LeTourneau, Y., Wang, Y. & Chopp, M. (2006). Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 26, 59966003.Google Scholar
Warfvinge, K., Kiilgaard, J.F., Klassen, H., Zamiri, P., Scherfig, E., Streilein, W., Prause, J.U. & Young, M.J. (2006). Retinal progenitor cell xenografts to the pig retina: Immunological reactions. Cell Transplantation 15, 603612.Google Scholar
Warre-Cornish, K., Barber, A.C., Sowden, J.C., Ali, R.R. & Pearson, R.A. (2013). Migration, integration and maturation of photoreceptor precursors following transplantation in the mouse retina. Stem Cells and Development 23, 941954.Google Scholar
Wenkel, H. & Streilein, J.W. (1998). Analysis of immune deviation elicited by antigens injected into the subretinal space. Investigative Ophthalmology & Visual Science 39, 18231834.Google Scholar
West, E.L., Gonzalez-Cordero, A., Hippert, C., Osakada, F., Martinez-Barbera, J.P., Pearson, R.A., Sowden, J.C., Takahashi, M. & Ali, R.R. (2012). Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors. Stem Cells 30, 14241435.Google Scholar
West, E.L., Pearson, R.A., Barker, S.E., Luhmann, U.F., Maclaren, R.E., Barber, A.C., Duran, Y., Smith, A.J., Sowden, J.C. & Ali, R.R. (2010). Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation. Stem Cells 28, 19972007.Google Scholar
West, E.L., Pearson, R.A., MacLaren, R.E., Sowden, J.C. & Ali, R.R. (2009). Cell transplantation strategies for retinal repair. Progress in Brain Research 175, 321.Google Scholar
West, E.L., Pearson, R.A., Tschernutter, M., Sowden, J.C., MacLaren, R.E. & Ali, R.R. (2008). Pharmacological disruption of the outer limiting membrane leads to increased retinal integration of transplanted photoreceptor precursors. Experimental Eye Research 86, 601611.Google Scholar
Wilbanks, G.A. & Streilein, J.W. (1990). Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and phenotypically distinct T-suppressor cell populations. Immunology 71, 383389.Google Scholar
Wojciechowski, A.B., Englund, U., Lundberg, C. & Warfvinge, K. (2002). Long-term survival and glial differentiation of the brain-derived precursor cell line RN33B after subretinal transplantation to adult normal rats. Stem Cells 20, 163173.Google Scholar
Yang, P., Seiler, M.J., Aramant, R.B. & Whittemore, S.R. (2002). Differential lineage restriction of rat retinal progenitor cells in vitro and in vivo. Journal of Neuroscience Research 69, 466476.Google Scholar
Young, M.J., Ray, J., Whiteley, S.J., Klassen, H. & Gage, F.H. (2000). Neuronal differentiation and morphological integration of hippocampal progenitor cells transplanted to the retina of immature and mature dystrophic rats. Molecular and Cellular Neurosciences 16, 197205.Google Scholar
Zhang, Y., Caffe, A.R., Azadi, S., van Veen, T., Ehinger, B. & Perez, M.T. (2003). Neuronal integration in an abutting-retinas culture system. Investigative Ophthalmology & Visual Science 44, 49364946.Google Scholar
Zhao, T., Zhang, Z.N., Rong, Z. & Xu, Y. (2011). Immunogenicity of induced pluripotent stem cells. Nature 474, 212215.Google Scholar