1932

Abstract

Recent advances in stem cell engineering have led to an explosion in the use of organoids as model systems for studies in multiple biological disciplines. Together with breakthroughs in genome engineering and the various omics, organoid technology is making possible studies of human biology that were not previously feasible. For vision science, retinal organoids derived from human stem cells allow differentiating and mature human retinal cells to be studied in unprecedented detail. In this review, we examine the technologies employed to generate retinal organoids and how organoids are revolutionizing the fields of developmental and cellular biology as they pertain to the retina. Furthermore, we explore retinal organoids from a clinical standpoint, offering a new platform with which to study retinal diseases and degeneration, test prospective drugs and therapeutic strategies, and promote personalized medicine. Finally, we discuss the range of possibilities that organoids may bring to future retinal research and consider their ethical implications.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-121219-081855
2020-09-15
2024-06-18
Loading full text...

Full text loading...

/deliver/fulltext/vision/6/1/annurev-vision-121219-081855.html?itemId=/content/journals/10.1146/annurev-vision-121219-081855&mimeType=html&fmt=ahah

Literature Cited

  1. Achberger K, Probst C, Haderspeck J, Bolz S, Rogal J et al. 2019. Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. eLife 8:e46188
    [Google Scholar]
  2. Adler R, Canto-Soler MV. 2007. Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies. Dev. Biol. 305:11–13
    [Google Scholar]
  3. Akhtar T, Xie H, Khan MI, Zhao H, Bao J et al. 2019. Accelerated photoreceptor differentiation of hiPSC-derived retinal organoids by contact co-culture with retinal pigment epithelium. Stem Cell Res 39:101491
    [Google Scholar]
  4. Altshuler D, Turco JJL, Rush J, Cepko C 1993. Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development 119:41317–28
    [Google Scholar]
  5. Al-Zamil WM, Yassin SA. 2017. Recent developments in age-related macular degeneration: a review. Clin. Interv. Aging 12:1313–30
    [Google Scholar]
  6. Ashapkin VV, Kutueva LI, Kurchashova SY, Kireev II 2019. Are there common mechanisms between the Hutchinson-Gilford progeria syndrome and natural aging. Front. Genet. 10:455
    [Google Scholar]
  7. Badea TC, Cahill H, Ecker J, Hattar S, Nathans J 2009. Distinct roles of transcription factors Brn3a and Brn3b in controlling the development, morphology, and function of retinal ganglion cells. Neuron 61:6852–64
    [Google Scholar]
  8. Barrett JR. 2005. Focusing on vision through an environmental lens. Environ. Health Perspect. 113:12A822–27
    [Google Scholar]
  9. Bernardos RL, Barthel LK, Meyers JR, Raymond PA 2007. Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. J. Neurosci. 27:267028–40
    [Google Scholar]
  10. Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B et al. 2019. Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat. Cell Biol. 21:81041–51
    [Google Scholar]
  11. Boucherie C, Mukherjee S, Henckaerts E, Thrasher AJ, Sowden JC, Ali RR 2012. Brief report: Self-organizing neuroepithelium from human pluripotent stem cells facilitates derivation of photoreceptors. Stem Cells 31:2408–14
    [Google Scholar]
  12. Braunger BM, Pielmeier S, Demmer C, Landstorfer V, Kawall D et al. 2013. TGF-β signaling protects retinal neurons from programmed cell death during the development of the mammalian eye. J. Neurosci. 33:3514246–58
    [Google Scholar]
  13. Bredenoord AL, Clevers H, Knoblich JA 2017. Human tissues in a dish: the research and ethical implications of organoid technology. Science 355:6322eaaf9414
    [Google Scholar]
  14. Browne AW, Arnesano C, Harutyunyan N, Khuu T, Martinez JC et al. 2017. Structural and functional characterization of human stem-cell-derived retinal organoids by live imaging. Investig. Ophthalmol. Vis. Sci. 58:93311–18
    [Google Scholar]
  15. Brzezinski JA, Lamba DA, Reh TA 2010. Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development. Development 137:4619–29
    [Google Scholar]
  16. Buskin A, Zhu L, Chichagova V, Basu B, Mozaffari-Jovin S et al. 2018. Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat. Commun. 9:4234
    [Google Scholar]
  17. Capowski EE, Samimi K, Mayerl SJ, Phillips MJ, Pinilla I et al. 2019. Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development 146:1dev171686
    [Google Scholar]
  18. Carter-Dawson LD, Lavail MM. 1979. Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine. J. Comp. Neurol. 188:2263–72
    [Google Scholar]
  19. Cayouette M, Poggi L, Harris WA 2006. Lineage in the vertebrate retina. Trends Neurosci 29:10563–70
    [Google Scholar]
  20. Chen HY, Welby E, Li T, Swaroop A 2019. Retinal disease in ciliopathies: recent advances with a focus on stem cell-based therapies. Transl. Sci. Rare Dis. 4:1–297–115
    [Google Scholar]
  21. Chichagova V, Dorgau B, Felemban M, Georgiou M, Armstrong L, Lako M 2019. Differentiation of retinal organoids from human pluripotent stem cells. Curr. Protoc. Stem Cell Biol. 50:1e95
    [Google Scholar]
  22. Clark BS, Stein-O'Brien GL, Shiau F, Cannon GH, Davis-Marcisak E et al. 2019. Single-cell RNA-seq analysis of retinal development identifies NFI factors as regulating mitotic exit and late-born cell specification. Neuron 102:61111–26.e5
    [Google Scholar]
  23. Clevers H. 2016. Modeling development and disease with organoids. Cell 165:71586–97
    [Google Scholar]
  24. Collin J, Queen R, Zerti D, Dorgau B, Hussain R et al. 2019. Deconstructing retinal organoids: single cell RNA-seq reveals the cellular components of human pluripotent stem cell-derived retina. Stem Cells 37:5593–98
    [Google Scholar]
  25. Cong L, Ran FA, Cox D, Lin S, Barretto R et al. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:6121819–23
    [Google Scholar]
  26. Cowan CS, Renner M, Gross-Scherf B, Goldblum D, Munz M et al. 2019. Cell types of the human retina and its organoids at single-cell resolution: developmental convergence, transcriptomic identity, and disease map. bioRxiv 703348. https://doi.org/10.1101/703348
    [Crossref] [Google Scholar]
  27. Daga FB, Ogata NG, Medeiros FA, Moran R, Morris J et al. 2018. Macular pigment and visual function in patients with glaucoma: the San Diego macular pigment study. Investig. Ophthalmol. Vis. Sci. 59:114471–76
    [Google Scholar]
  28. Daiger SP, Rossiter BJF, Greenberg J, Christoffels A, Hide W 1998. Data services and software for identifying genes and mutations causing retinal degeneration. Investig. Ophthalmol. Vis. Sci. 39:S295
    [Google Scholar]
  29. Demb JB, Singer JH. 2015. Functional circuitry of the retina. Annu. Rev. Vis. Sci. 1:263–89
    [Google Scholar]
  30. Deng WL, Gao ML, Lei XL, Lv JN, Zhao H et al. 2018. Gene correction reverses ciliopathy and photoreceptor loss in iPSC-derived retinal organoids from retinitis pigmentosa patients. Stem Cell Rep 10:41267–81
    [Google Scholar]
  31. DiStefano T, Chen HY, Panebianco C, Kaya KD, Brooks MJ et al. 2018. Accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors. Stem Cell Rep 10:1300–13
    [Google Scholar]
  32. Dyer MA, Cepko CL. 2001. Regulating proliferation during retinal development. Nat. Rev. Neurosci. 2:5333–42
    [Google Scholar]
  33. Eldred KC, Hadyniak SE, Hussey KA, Brenerman B, Zhang P-W et al. 2018. Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science 362:6411eaau6348
    [Google Scholar]
  34. Fausett BV, Gumerson JD, Goldman D 2008. The proneural basic helix-loop-helix gene Ascl1a is required for retina regeneration. J. Neurosci. 28:51109–17
    [Google Scholar]
  35. Fligor CM, Langer KB, Sridhar A, Ren Y, Shields PK et al. 2018. Three-dimensional retinal organoids facilitate the investigation of retinal ganglion cell development, organization and neurite outgrowth from human pluripotent stem cells. Sci. Rep. 8:114520
    [Google Scholar]
  36. Freund C, Horsford DJ, McInnes RR 1996. Transcription factor genes and the developing eye: a genetic perspective. Hum. Mol. Genet. 5:Suppl. 11471–88
    [Google Scholar]
  37. Frobel J, Hemeda H, Lenz M, Abagnale G, Joussen S et al. 2014. Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells. Stem Cell Rep 3:3414–22
    [Google Scholar]
  38. Gagliardi G, Ben M'Barek K, Chaffiol A, Slembrouck-Brec A, Conart J-B et al. 2018. Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids. Stem Cell Rep 11:3665–80
    [Google Scholar]
  39. Gamm DM, Wong R. 2015. Report on the National Eye Institute Audacious Goals Initiative: photoreceptor regeneration and integration workshop. Trans. Vis. Sci. Tech. 4:62
    [Google Scholar]
  40. Gao L, Chen X, Zeng Y, Li Q, Zou T et al. 2016. Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells. Sci. Rep. 6:29944
    [Google Scholar]
  41. Giannelli SG, Demontis GC, Pertile G, Rama P, Broccoli V 2011. Adult human Müller glia cells are a highly efficient source of rod photoreceptors. Stem Cells 29:2344–56
    [Google Scholar]
  42. Gonzalez-Cordero A, Kruczek K, Naeem A, Fernando M, Kloc M et al. 2017. Recapitulation of human retinal development from human pluripotent stem cells generates transplantable populations of cone photoreceptors. Stem Cell Rep 9:3820–37
    [Google Scholar]
  43. Hendrickson A. 2016. Development of retinal layers in prenatal human retina. Am. J. Ophthalmol. 161:29–35.e1
    [Google Scholar]
  44. Hinds JW, Hinds PL. 1979. Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis. J. Comp. Neurol. 187:3495–511
    [Google Scholar]
  45. Hochmann S, Kaslin J, Hans S, Weber A, Machate A et al. 2012. Fgf signaling is required for photoreceptor maintenance in the adult zebrafish retina. PLOS ONE 7:1e30365
    [Google Scholar]
  46. Hoshino A, Ratnapriya R, Brooks MJ, Chaitankar V, Wilken MS et al. 2017. Molecular anatomy of the developing human retina. Dev. Cell. 43:6763–79.e4
    [Google Scholar]
  47. Hu Y, Wang X, Hu B, Mao Y, Chen Y et al. 2019. Dissecting the transcriptome landscape of the human fetal neural retina and retinal pigment epithelium by single-cell RNA-seq analysis. PLOS Biol 17:7e3000365
    [Google Scholar]
  48. Islam MR, Nakamura K, Casco-Robles MM, Kunahong A, Inami W et al. 2014. The newt reprograms mature RPE cells into a unique multipotent state for retinal regeneration. Sci. Rep. 4:6043
    [Google Scholar]
  49. Jadhav AP, Mason HA, Cepko CL 2006. Notch 1 inhibits photoreceptor production in the developing mammalian retina. Development 133:5913–23
    [Google Scholar]
  50. Jensen AM, Wallace VA. 1997. Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina. Development 124:2363–71
    [Google Scholar]
  51. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:6096816–21
    [Google Scholar]
  52. Jorstad NL, Wilken MS, Grimes WN, Wohl SG, VandenBosch LS et al. 2017. Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548:7665103–7
    [Google Scholar]
  53. Katoh K, Omori Y, Onishi A, Sato S, Kondo M, Furukawa T 2010. Blimp1 suppresses Chx10 expression in differentiating retinal photoreceptor precursors to ensure proper photoreceptor development. J. Neurosci. 30:196515–26
    [Google Scholar]
  54. Kedzierski W, Bok D, Travis GH 1998. Non-cell-autonomous photoreceptor degeneration in rds mutant mice mosaic for expression of a rescue transgene. J. Neurosci. 18:114076–82
    [Google Scholar]
  55. Keller G. 2005. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 19:101129–55
    [Google Scholar]
  56. Kim M, Mun H, Sung CO, Cho EJ, Jeon H-J et al. 2019a. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat. Commun. 10:13991
    [Google Scholar]
  57. Kim S, Lowe A, Dharmat R, Lee S, Owen LA et al. 2019b. Generation, transcriptome profiling, and functional validation of cone-rich human retinal organoids. PNAS 116:2210824–33
    [Google Scholar]
  58. Koenekoop RK. 2004. An overview of leber congenital amaurosis: a model to understand human retinal development. Surv. Ophthalmol. 49:4379–98
    [Google Scholar]
  59. Koike H, Iwasawa K, Ouchi R, Maezawa M, Giesbrecht K et al. 2019. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature 574:7776112–16
    [Google Scholar]
  60. 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. Nat. Commun. 6:6286
    [Google Scholar]
  61. Laboissonniere LA, Goetz JJ, Martin GM, Bi R, Lund TJS et al. 2019. Molecular signatures of retinal ganglion cells revealed through single cell profiling. Sci. Rep. 9:115778
    [Google Scholar]
  62. Lake N. 1994. Taurine and GABA in the rat retina during postnatal development. Vis. Neurosci. 11:2253–60
    [Google Scholar]
  63. Lakowski J, Welby E, Budinger D, Di Marco F, Di Foggia V et al. 2018. Isolation of human photoreceptor precursors via a cell surface marker panel from stem cell‐derived retinal organoids and fetal retinae. Stem Cells 36:5709–22
    [Google Scholar]
  64. Lam PT, Gutierrez C, Del Rio-Tsonis K, Robinson ML 2019. Generation of a retina reporter hiPSC line to label progenitor, ganglion, and photoreceptor cell types. bioRxiv 658963. https://doi.org/10.1101/658963
    [Crossref] [Google Scholar]
  65. Lancaster MA, Knoblich JA. 2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:61941247125
    [Google Scholar]
  66. Lapasset L, Milhavet O, Prieur A, Besnard E, Babled A et al. 2011. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev 25:212248–53
    [Google Scholar]
  67. Le R, Kou Z, Jiang Y, Li M, Huang B et al. 2014. Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells. Cell Stem Cell 14:127–39
    [Google Scholar]
  68. Levine EM, Roelink H, Turner J, Reh TA 1997. Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J. Neurosci. 17:166277–88
    [Google Scholar]
  69. Liu H, Thurig S, Mohamed O, Dufort D, Wallace VA 2006. Mapping canonical Wnt signaling in the developing and adult retina. Investig. Ophthalmol. Vis. Sci. 47:115088–97
    [Google Scholar]
  70. Locker M, Agathocleous M, Amato MA, Parain K, Harris WA, Perron M 2006. Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors. Genes Dev 20:213036–48
    [Google Scholar]
  71. Lombardini JB. 1991. Taurine: retinal function. Brain Res. Rev. 16:151–69
    [Google Scholar]
  72. 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 Rep 6:5743–56
    [Google Scholar]
  73. Lu Y, Yi W, Wu Q, Zhong S, Zuo Z et al. 2018. Single-cell RNA-seq analysis maps the development of human fetal retina. bioRxiv 423830. https://doi.org/10.1101/423830
    [Crossref] [Google Scholar]
  74. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:51202–14
    [Google Scholar]
  75. Mansergh FC, Carrigan M, Hokamp K, Farrar GJ 2015. Gene expression changes during retinal development and rod specification. Mol. Vis. 21:61–87
    [Google Scholar]
  76. Mao X, An Q, Xi H, Yang X-J, Zhang X et al. 2019. Single-cell RNA sequencing of hESC-derived 3D retinal organoids reveals novel genes regulating RPC commitment in early human retinogenesis. Stem Cell Rep 13:4747–60
    [Google Scholar]
  77. Martinez-Morales J-R, Del Bene F, Nica G, Hammerschmidt M, Bovolenta P, Wittbrodt J 2005. Differentiation of the vertebrate retina is coordinated by an FGF signaling center. Dev. Cell. 8:4565–74
    [Google Scholar]
  78. Masai I, Yamaguchi M, Tonou-Fujimori N, Komori A, Okamoto H 2005. The hedgehog-PKA pathway regulates two distinct steps of the differentiation of retinal ganglion cells: the cell-cycle exit of retinoblasts and their neuronal maturation. Development 132:71539–53
    [Google Scholar]
  79. Masland RH. 2012. The neuronal organization of the retina. Neuron 76:2266–80
    [Google Scholar]
  80. Masuda T, Zhang X, Berlinicke C, Wan J, Yerrabelli A et al. 2014. The transcription factor GTF2IRD1 regulates the topology and function of photoreceptors by modulating photoreceptor gene expression across the retina. J. Neurosci. 34:4615356–68
    [Google Scholar]
  81. McLelland BT, Lin B, Mathur A, Aramant RB, Thomas BB et al. 2018. Transplanted hESC-derived retina organoid sheets differentiate, integrate, and improve visual function in retinal degenerate rats. Investig. Ophthalmol. Vis. Sci. 59:62586–603
    [Google Scholar]
  82. McLeod DS, Hasegawa T, Prow T, Merges C, Lutty G 2006. The initial fetal human retinal vasculature develops by vasculogenesis. Dev. Dyn. 235:123336–47
    [Google Scholar]
  83. Megaw R, Abu-Arafeh H, Jungnickel M, Mellough C, Gurniak C et al. 2017. Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models. Nat. Commun. 8:1271
    [Google Scholar]
  84. Mellough CB, Bauer R, Collin J, Dorgau B, Zerti D et al. 2019a. An integrated transcriptional analysis of the developing human retina. Development 146:2dev169474
    [Google Scholar]
  85. Mellough CB, Collin J, Queen R, Hilgen G, Dorgau B et al. 2019b. Systematic comparison of retinal organoid differentiation from human pluripotent stem cells reveals stage specific, cell line, and methodological differences. Stem Cells Transl. Med. 8:7694–706
    [Google Scholar]
  86. Meyer JS, Howden SE, Wallace KA, Verhoeven AD, Wright LS et al. 2011. Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells 29:81206–18
    [Google Scholar]
  87. Meyer JS, Shearer RL, Capowski EE, Wright LS, Wallace KA et al. 2009. Modeling early retinal development with human embryonic and induced pluripotent stem cells. PNAS 106:3916698–703
    [Google Scholar]
  88. Meyers JR, Hu L, Moses A, Kaboli K, Papandrea A, Raymond PA 2012. β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina. Neural Dev 7:30
    [Google Scholar]
  89. Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B et al. 2013. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13:6691–705
    [Google Scholar]
  90. Mills EA, Goldman D. 2017. The regulation of Notch signaling in retinal development and regeneration. Curr. Pathobiol. Rep. 5:4323–31
    [Google Scholar]
  91. Munsie M, Hyun I, Sugarman J 2017. Ethical issues in human organoid and gastruloid research. Development 144:6942–45
    [Google Scholar]
  92. Murali D, Yoshikawa S, Corrigan RR, Plas DJ, Crair MC et al. 2005. Distinct developmental programs require different levels of Bmp signaling during mouse retinal development. Development 132:5913–23
    [Google Scholar]
  93. Nakano T, Ando S, Takata N, Kawada M, Muguruma K et al. 2012. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10:6771–85
    [Google Scholar]
  94. Nath M, Halder N, Velpandian T 2017. Circulating biomarkers in glaucoma, age-related macular degeneration, and diabetic retinopathy. Indian J. Ophthalmol. 65:3191–97
    [Google Scholar]
  95. Ng L, Hurley JB, Dierks B, Srinivas M, Saltó C et al. 2001. A thyroid hormone receptor that is required for the development of green cone photoreceptors. Nat. Genet. 27:194–98
    [Google Scholar]
  96. Norden C, Young S, Link BA, Harris WA 2009. Actomyosin is the main driver of interkinetic nuclear migration in the retina. Cell 138:61195–208
    [Google Scholar]
  97. O'Brien KMB, Cheng H, Jiang Y, Schulte D, Swaroop A, Hendrickson AE 2004. Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Investig. Opthalmol. Vis. Sci. 45:82807–12
    [Google Scholar]
  98. Ohlemacher SK, Iglesias CL, Sridhar A, Gamm DM, Meyer JS 2015. Generation of highly enriched populations of optic vesicle−like retinal cells from human pluripotent stem cells. Curr. Protoc. Stem Cell Biol. 32:1 1H.8.1–20
    [Google Scholar]
  99. Organisciak DT, Vaughan DK. 2010. Retinal light damage: mechanisms and protection. Prog. Retin. Eye Res. 29:2113–34
    [Google Scholar]
  100. Ortín-Martínez A, Nadal-Nicolás FM, Jiménez-López M, Alburquerque-Béjar JJ, Nieto-López L et al. 2014. Number and distribution of mouse retinal cone photoreceptors: differences between an albino (Swiss) and a pigmented (C57/BL6) strain. PLOS ONE 9:7e102392
    [Google Scholar]
  101. Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K et al. 2008a. Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat. Biotechnol. 26:2215–24
    [Google Scholar]
  102. Osakada F, Ikeda H, Watanabe K, Akaike A, Sasai Y, Takahashi M 2008b. Differentiation of rod and cone photoreceptors from human embryonic stem cells under defined culture conditions. Investig. Ophthalmol. Vis. Sci. 49:133566
    [Google Scholar]
  103. Ovando-Roche P, West EL, Branch MJ, Sampson RD, Fernando M et al. 2018. Use of bioreactors for culturing human retinal organoids improves photoreceptor yields. Stem Cell Res. Ther. 9:1156
    [Google Scholar]
  104. Parfitt DA, Lane A, Ramsden CM, Carr A-JF, Munro PM et al. 2016. Identification and correction of mechanisms underlying inherited blindness in human iPSC-derived optic cups. Cell Stem Cell 18:6769–81
    [Google Scholar]
  105. Peng Y-R, Shekhar K, Yan W, Herrmann D, Sappington A et al. 2019. Molecular classification and comparative taxonomics of foveal and peripheral cells in primate retina. Cell 176:51222–37.e22
    [Google Scholar]
  106. Phan N, Hong JJ, Tofig B, Mapua M, Elashoff D et al. 2019. A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids. Commun. Biol. 2:78
    [Google Scholar]
  107. Pollak J, Wilken MS, Ueki Y, Cox KE, Sullivan JM et al. 2013. ASCL1 reprograms mouse Müller glia into neurogenic retinal progenitors. Development 140:122619–31
    [Google Scholar]
  108. Provis JM, Dubis AM, Maddess T, Carroll J 2013. Adaptation of the central retina for high acuity vision: cones, the fovea and the avascular zone. Prog. Retin. Eye Res. 35:63–81
    [Google Scholar]
  109. Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia A-S et al. 2001. The retina. Neuroscience D Purves, GJ Augustine, D Fitzpatrick, LC Katz, A-S LaMantia, JO McNamara, SM Williams, art. 100 Sunderland, MA: Sinauer Assoc. , 2nd ed..
    [Google Scholar]
  110. Quinn PM, Buck TM, Mulder AA, Ohonin C, Alves CH et al. 2019. Human iPSC-derived retinas recapitulate the fetal CRB1 CRB2 complex formation and demonstrate that photoreceptors and Müller glia are targets of AAV5. Stem Cell Rep 12:5906–19
    [Google Scholar]
  111. Radisic M. 2019. Building a better model of the retina. eLife 8:e51183
    [Google Scholar]
  112. Reese BE. 2011. Development of the retina and optic pathway. Vis. Res. 51:7613–32
    [Google Scholar]
  113. Reichman S, Terray A, Slembrouck A, Nanteau C, Orieux G et al. 2014. From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium. PNAS 111:238518–23
    [Google Scholar]
  114. Remez LA, Onishi A, Menuchin-Lasowski Y, Biran A, Blackshaw S et al. 2017. Pax6 is essential for the generation of late-born retinal neurons and for inhibition of photoreceptor-fate during late stages of retinogenesis. Dev. Biol. 432:1140–50
    [Google Scholar]
  115. Rheaume BA, Jereen A, Bolisetty M, Sajid MS, Yang Y et al. 2018. Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes. Nat. Commun. 9:12759
    [Google Scholar]
  116. Russell S, Bennett J, Wellman JA, Chung DC, Yu Z-F et al. 2017. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet 390:10097849–60
    [Google Scholar]
  117. Shao J, Zhou P-Y, Peng G-H 2017. Experimental study of the biological properties of human embryonic stem cell-derived retinal progenitor cells. Sci. Rep. 7:42363
    [Google Scholar]
  118. Sharma TP, Wiley LA, Whitmore SS, Anfinson KR, Cranston CM et al. 2017. Patient-specific induced pluripotent stem cells to evaluate the pathophysiology of TRNT1-associated retinitis pigmentosa. Stem Cell Res 21:58–70
    [Google Scholar]
  119. Shekhar K, Lapan SW, Whitney IE, Tran NM, Macosko EZ et al. 2016. Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics. Cell 166:51308–23.e30
    [Google Scholar]
  120. Shibusawa N, Hashimoto K, Nikrodhanond AA, Liberman MC, Applebury ML et al. 2003. Thyroid hormone action in the absence of thyroid hormone receptor DNA-binding in vivo. J. Clin. Investig. 112:4588–97
    [Google Scholar]
  121. Shrestha R, Wen Y-T, Ding D-C, Tsai R-K 2019. Aberrant hiPSCs-derived from human keratinocytes differentiates into 3D retinal organoids that acquire mature photoreceptors. Cells 8:1E36
    [Google Scholar]
  122. Singh RK, Mallela RK, Cornuet PK, Reifler AN, Chervenak AP et al. 2015. Characterization of three-dimensional retinal tissue derived from human embryonic stem cells in adherent monolayer cultures. Stem Cells Dev 24:232778–95
    [Google Scholar]
  123. Singh RK, Occelli LM, Binette F, Petersen-Jones SM, Nasonkin IO 2019. Transplantation of human embryonic stem cell-derived retinal tissue in the subretinal space of the cat eye. Stem Cells Dev 28:171151–66
    [Google Scholar]
  124. Slijkerman RWN, Song F, Astuti GDN, Huynen MA, van Wijk E et al. 2015. The pros and cons of vertebrate animal models for functional and therapeutic research on inherited retinal dystrophies. Prog. Retin. Eye Res. 48:137–59
    [Google Scholar]
  125. Sluch VM, Chamling X, Liu MM, Berlinicke CA, Cheng J et al. 2017. Enhanced stem cell differentiation and immunopurification of genome engineered human retinal ganglion cells. Stem Cells Transl. Med. 6:111972–86
    [Google Scholar]
  126. Sluch VM, Davis CO, Ranganathan V, Kerr JM, Krick K et al. 2015. Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line. Sci. Rep. 5:16595
    [Google Scholar]
  127. Steinfeld J, Steinfeld I, Bausch A, Coronato N, Hampel M-L et al. 2017. BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling. Biol. Open 6:7979–92
    [Google Scholar]
  128. Stenkamp DL. 2015. Development of the vertebrate eye and retina. Prog. Mol. Biol. Transl. Sci. 134:397–414
    [Google Scholar]
  129. Sugarman J, Bredenoord AL. 2019. Reflections on organoid ethics: Jeremy Sugarman and Annelien Bredenoord. Cell Stem Cell 24:6849–51
    [Google Scholar]
  130. Swinney DC, Anthony J. 2011. How were new medicines discovered. Nat. Rev. Drug Discov. 10:7507–19
    [Google Scholar]
  131. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:5861–72
    [Google Scholar]
  132. Teotia P, Van Hook MJ, Wichman CS, Allingham RR, Hauser MA, Ahmad I 2017. Modeling glaucoma: retinal ganglion cells generated from induced pluripotent stem cells of patients with SIX6 risk allele show developmental abnormalities. Stem Cells 35:112239–52
    [Google Scholar]
  133. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:53911145–47
    [Google Scholar]
  134. Tucker BA, Mullins RF, Streb LM, Anfinson K, Eyestone ME et al. 2013. Patient-specific iPSC-derived photoreceptor precursor cells as a means to investigate retinitis pigmentosa. eLife 2:e00824
    [Google Scholar]
  135. Uygun BE, Sharma N, Yarmush M 2009. Retinal pigment epithelium differentiation of stem cells: current status and challenges. Crit. Rev. Biomed. Eng. 37:355–75
    [Google Scholar]
  136. van Norren D, Vos JJ 2016. Light Damage to the Retina: An Historical Approach Berlin: Nat. Publ. Group
    [Google Scholar]
  137. Völkner M, Zschätzsch M, Rostovskaya M, Overall RW, Busskamp V et al. 2016. Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem Cell Rep 6:4525–38
    [Google Scholar]
  138. Volland S, Esteve-Rudd J, Hoo J, Yee C, Williams DS 2015. A comparison of some organizational characteristics of the mouse central retina and the human macula. PLOS ONE 10:4e0125631
    [Google Scholar]
  139. Wahlin KJ, Maruotti JA, Sripathi SR, Ball J, Angueyra JM et al. 2017. Photoreceptor outer segment-like structures in long-term 3D retinas from human pluripotent stem cells. Sci. Rep. 7:1766
    [Google Scholar]
  140. Walshe TE, Leach LL, D'Amore PA 2011. TGF-β signaling is required for maintenance of retinal ganglion cell differentiation and survival. Neuroscience 189:123–31
    [Google Scholar]
  141. Wang H, La Russa M, Qi LS 2016. CRISPR/Cas9 in genome editing and beyond. Annu. Rev. Biochem. 85:227–64
    [Google Scholar]
  142. Wang S, Sengel C, Emerson MM, Cepko CL 2014. A gene regulatory network controls the binary fate decision of rod and bipolar cells in the vertebrate retina. Dev. Cell. 30:5513–27
    [Google Scholar]
  143. Weeber F, Ooft SN, Dijkstra KK, Voest EE 2017. Tumor organoids as a pre-clinical cancer model for drug discovery. Cell Chem. Biol. 24:91092–100
    [Google Scholar]
  144. Welby E, Lakowski J, Di Foggia V, Budinger D, Gonzalez-Cordero A et al. 2017. Isolation and comparative transcriptome analysis of human fetal and iPSC-derived cone photoreceptor cells. Stem Cell Rep 9:61898–915
    [Google Scholar]
  145. Wnorowski A, Yang H, Wu JC 2019. Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models. Adv. Drug Deliv. Rev. 140:3–11
    [Google Scholar]
  146. Zagozewski JL, Zhang Q, Pinto VI, Wigle JT, Eisenstat DD 2014. The role of homeobox genes in retinal development and disease. Dev. Biol. 393:2195–208
    [Google Scholar]
  147. Zhong X, Gutierrez C, Xue T, Hampton C, Vergara MN et al. 2014. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat. Commun. 5:4047
    [Google Scholar]
  148. Zhou S, Flamier A, Abdouh M, Tétreault N, Barabino A et al. 2015. Differentiation of human embryonic stem cells into cone photoreceptors through simultaneous inhibition of BMP, TGFβ and Wnt signaling. Development 142:193294–306
    [Google Scholar]
/content/journals/10.1146/annurev-vision-121219-081855
Loading
/content/journals/10.1146/annurev-vision-121219-081855
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error