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Stem Cell Therapies in the Management of Diabetic Retinopathy

  • Transplantation (A Pileggi, Section Editor)
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Abstract

Diabetic retinopathy is the leading cause of blindness in the working population. We now understand that the pathogenesis of the disease contains both a neurodegenerative and vasodegenerative component. Yet despite this, current treatment is still limited to combating the proliferative end stage component of the disease rather than addressing its underlying causes. In recent years, much basic research has focused on demonstrating the potential that several classes of stem cells have in conferring both neuro- and vasoprotection on the diabetic retina. Further, progress has been made in using stem cells to stimulate both neuro and vascular regeneration. This review will discuss the current understanding as to what mechanisms underlie diabetic retinopathy while highlighting the types of stem cells which offer hope as potential novel therapies for diabetic retinopathy, including those that are now in clinical trial.

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References

  1. Fong D, Aiello L, Gardner T, King G, Blankenship G, Cavallerano J, et al. Retinopathy in diabetes. Diabetes Care. 2004;27 Suppl 1:S84–7.

    Article  PubMed  Google Scholar 

  2. Stitt A, O'Neill C, O'Doherty M, Archer D, Gardiner T, Medina R. Vascular stem cells and ischaemic retinopathies. Prog Retin Eye Res. 2011;30(3):149–66.

    Article  CAS  PubMed  Google Scholar 

  3. Shaw J, Sicree R, Zimmet P. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.

    Article  CAS  PubMed  Google Scholar 

  4. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel G, et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004;82(11):844–51.

    PubMed Central  PubMed  Google Scholar 

  5. Sharma N, Gardiner T, Archer D. A morphologic and autoradiographic study of cell death and regeneration in the retinal microvasculature of normal and diabetic rats. Am J Ophthalmol. 1985;100(1):51–60.

    Article  CAS  PubMed  Google Scholar 

  6. Semenza G. HIF-1 and human disease: one highly involved factor. Genes Dev. 2000;14(16):1983–91.

    CAS  PubMed  Google Scholar 

  7. Aiello L, Avery R, Arrigg P, Keyt B, Jampel H, Shah S, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331(22):1480–7.

    Article  CAS  PubMed  Google Scholar 

  8. Barber A. A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuro-Psychopharmacol Biol Psychiatry. 2003;27(2):283–90.

    Article  CAS  Google Scholar 

  9. Gardner T, Antonetti D, Barber A, LaNoue K, Levison S. Diabetic retinopathy: more than meets the eye. Surv Ophthalmol. 2002;47 Suppl 2:S253–62.

    Article  PubMed  Google Scholar 

  10. Antonetti D, Barber A, Bronson S, Freeman W, Gardner T, Jefferson L, et al. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes. 2006;55(9):2401–11.

    Article  CAS  PubMed  Google Scholar 

  11. Tzekov R, Arden G. The electroretinogram in diabetic retinopathy. Surv Ophthalmol. 1999;44(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  12. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 352(9131):837–53.

  13. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med. 2000 342(6):381–9.

  14. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 352(9131):854–65.

  15. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 329(14):977–86.

  16. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 98(5 Suppl):757–65.

  17. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 98(5 Suppl):766–85.

  18. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 103(12):1796–806.

  19. Aiello L. Perspectives on diabetic retinopathy. Am J Ophthalmol. 2003;136(1):122–35.

    Article  PubMed  Google Scholar 

  20. Porada C, Zanjani E, Almeida-Porad G. Adult mesenchymal stem cells: a pluripotent population with multiple applications. Curr Stem Cell Res Ther. 2006;1(3):365–9.

    Article  CAS  PubMed  Google Scholar 

  21. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007;25(11):2739–49.

    Article  CAS  PubMed  Google Scholar 

  22. Prockop D. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276(5309):71–4.

    Article  CAS  PubMed  Google Scholar 

  23. Abdi R, Fiorina P, Adra C, Atkinson M, Sayegh M. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57(7):1759–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Nauta A, Fibbe W. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110(10):3499–506.

    Article  CAS  PubMed  Google Scholar 

  25. Caplan A, Dennis J. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–84.

    Article  CAS  PubMed  Google Scholar 

  26. Kicic A, Shen W, Wilson A, Constable I, Robertson T, Rakoczy P. Differentiation of marrow stromal cells into photoreceptors in the rat eye. J Neurosci. 2003;23(21):7742–9.

    CAS  PubMed  Google Scholar 

  27. Tomita M, Adachi Y, Yamada H, Takahashi K, Kiuchi K, Oyaizu H, et al. Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina. Stem Cells. 2002;20(4):279–83.

    Article  CAS  PubMed  Google Scholar 

  28. Gong L, Wu Q, Song B, Lu B, Zhang Y. Differentiation of rat mesenchymal stem cells transplanted into the subretinal space of sodium iodate-injected rats. Clin Experiment Ophthalmol. 2008;36(7):666–71.

    Article  PubMed  Google Scholar 

  29. Wang S, Lu, Girman S, Duan J, McFarland T, Zhang Q, et al. Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology. PLoS ONE. 2010;5(2):e9200.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Lund R, Wang S, Lu B, Girman S, Holmes T, Sauvé Y, et al. Cells isolated from umbilical cord tissue rescue photoreceptors and visual functions in a rodent model of retinal disease. Stem Cells. 2007;25(3):602–11.

    Article  CAS  PubMed  Google Scholar 

  31. Davatchi F, Nikbin B, Shams H, Abdollahi B, Mohyeddin M, Shahram F. Mesenchymal stem cell therapy unable to rescue the vision from advanced Behcet's disease retinal vasculitis: report of three patients. Int J Rheum Dis. 2013;16(2):139–47.

    Article  CAS  PubMed  Google Scholar 

  32. Siqueira R, Jorge R. Translational research in retinology. Clin Ophthalmol. 2011;5:1493–8.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Li L, Xia Y, Wang Z, Cao X, Zhanyun, Guo G, et al. Suppression of the PI3K-Akt pathway is involved in the decreased adhesion and migration of bone marrow-derived mesenchymal stem cells from non-obese diabetic mice. Cell Biol Int. 2011;35(9):961–6.

    Article  CAS  PubMed  Google Scholar 

  34. Xu Y, Gu Z, Shen B, Xu G, Zhou T, Jiang J, et al. Roles of Wnt/β-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice. J Mol Neurosci. 2013;49(2):250–61.

    Article  CAS  PubMed  Google Scholar 

  35. Jiang X, Zhang Y, Liu B, Zhang S, Wu Y, Yu X, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120–6.

    Article  CAS  PubMed  Google Scholar 

  36. Aggarwal S, Pittenger M. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–22.

    Article  CAS  PubMed  Google Scholar 

  37. Volarevic V, Arsenijevic N, Lukic M, Stojkovic M. Concise review: mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells. 2011;29(1):5–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Volarevic V, Al-Qahtani A, Arsenijevic N, Pajovic S, Lukic M. Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis. Autoimmunity. 2010;43(4):255–63.

    Article  CAS  PubMed  Google Scholar 

  39. Fiorina P, Jurewicz M, Augello A, Vergani A, Dada S, Rosa S, et al. Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes. J Immunol. 2009;183(2):993–1004.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Ejaz S, Chekarova I, Ejaz A, Sohail A, Lim C. Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes Metab. 2008;10(1):53–63.

    CAS  PubMed  Google Scholar 

  41. Salmon A, Pérez V, Bokov A, Jernigan A, Kim G, Zhao H, et al. Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span. FASEB J. 2009;23(10):3601–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, et al. Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther. 2005;11(1):96–104.

    Article  CAS  PubMed  Google Scholar 

  43. Li Y, Chen J, Zhang C, Wang L, Lu D, Katakowski M, et al. Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia. 2005;49(3):407–17.

    Article  PubMed  Google Scholar 

  44. Li N, Li X, Yuan J. Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol. 2009;247(4):503–14.

    Article  PubMed  Google Scholar 

  45. Zhang Y, Wang W. Effects of bone marrow mesenchymal stem cell transplantation on light-damaged retina. Invest Ophthalmol Vis Sci. 2010;51(7):3742–8.

    Article  PubMed  Google Scholar 

  46. Inoue Y, Iriyama A, Ueno S, Takahashi H, Kondo M, Tamaki Y, et al. Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp Eye Res. 2007;85(2):234–41.

    Article  CAS  PubMed  Google Scholar 

  47. Asahara T, Murohara T, Sullivan A, Silver M, Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.

    Article  CAS  PubMed  Google Scholar 

  48. Jiang S, Walker L, Afentoulis M, Anderson D, Jauron-Mills L, Corless C, et al. Transplanted human bone marrow contributes to vascular endothelium. Proc Natl Acad Sci U S A. 2004;101(48):16891–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Yoder M, Ingram D. The definition of EPCs and other bone marrow cells contributing to neoangiogenesis and tumor growth: is there common ground for understanding the roles of numerous marrow-derived cells in the neoangiogenic process? Biochim Biophys Acta. 2009;1796(1):50–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Peichev M, Naiyer A, Pereira D, Zhu Z, Lane W, Williams M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952–8.

    CAS  PubMed  Google Scholar 

  51. Fadini G, Losordo D, Dimmeler S. Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use. Circ Res. 2012;110(4):624–37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Hill J, Zalos G, Halcox J, Schenke W, Waclawiw M, Quyyumi A, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348(7):593–600.

    Article  PubMed  Google Scholar 

  53. Timmermans F, Plum J, Yöder M, Ingram D, Vandekerckhove B, Case J. Endothelial progenitor cells: identity defined? J Cell Mol Med. 2009;13(1):87–102.

    Article  PubMed  Google Scholar 

  54. Ingram D, Mead L, Tanaka H, Meade V, Fenoglio A, Mortell K, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104(9):2752–60.

    Article  CAS  PubMed  Google Scholar 

  55. Yoder M, Mead L, Prater D, Krier T, Mroueh K, Li F, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109(5):1801–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Medina R, O'Neill C, Sweeney M, Guduric-Fuchs J, Gardiner T, Simpson D, et al. Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities. BMC Med Genomics. 2010;3:18.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Otani A, Kinder K, Ewalt K, Otero F, Schimmel P, Friedlander M. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med. 2002;8(9):1004–10.

    Article  CAS  PubMed  Google Scholar 

  58. Caballero S, Sengupta N, Afzal A, Chang K, Calzi S, Guberski D, et al. Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes. 2007;56(4):960–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Zhang W, Yan H. Dysfunction of circulating endothelial progenitor cells in type 1 diabetic rats with diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2013;251(4):1123–31.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang W, Yan H. Simvastatin increases circulating endothelial progenitor cells and reduces the formation and progression of diabetic retinopathy in rats. Exp Eye Res. 2012;105:1–8.

    Article  CAS  PubMed  Google Scholar 

  61. Loomans C, Koning E, Staal F, Rookmaaker M, Verseyden C, Boer H, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53(1):195–9.

    Article  CAS  PubMed  Google Scholar 

  62. Sibal L, Aldibbiat A, Agarwal S, Mitchell G, Oates C, Razvi S, et al. Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia. 2009;52(8):1464–73.

    Article  CAS  PubMed  Google Scholar 

  63. Medina R, O'Neill C, Devine A, Gardiner T, Stitt A. The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies. PLoS ONE. 2008;3(7):e2584.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Weis M, Heeschen C, Glassford A, Cooke J. Statins have biphasic effects on angiogenesis. Circulation. 2002;105(6):739–45.

    Article  CAS  PubMed  Google Scholar 

  65. Gaede P, Lund-Andersen H, Parving H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.

    Article  CAS  PubMed  Google Scholar 

  66. Chew E, Ambrosius W, Davis M, Danis R, Gangaputra S, Greven C, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233–44.

    Article  PubMed  Google Scholar 

  67. Connor K, SanGiovanni J, Lofqvist C, Aderman C, Chen J, Higuchi A, et al. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007;13(7):868–73.

    Article  CAS  PubMed  Google Scholar 

  68. Tikhonenko M, Lydic T, Opreanu M, Calzi S, Bozack S, McSorley K, et al. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function. PLoS ONE. 2013;8(1):e55177.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. He T, Lu T, D'Uscio L, Lam C, Lee H, Katusic Z. Angiogenic function of prostacyclin biosynthesis in human endothelial progenitor cells. Circ Res. 2008;103(1):80–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Rehman J, Li J, Orschell C, March K. Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107(8):1164–9.

    Article  PubMed  Google Scholar 

  71. Yoon C, Hur J, Park K, Kim J, Lee C, Oh I, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation. 2005;112(11):1618–27.

    Article  PubMed  Google Scholar 

  72. Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355(12):1199–209.

    Article  CAS  PubMed  Google Scholar 

  73. Aicher A, Brenner W, Zuhayra M, Badorff C, Massoudi S, Assmus B, et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation. 2003;107(16):2134–9.

    Article  PubMed  Google Scholar 

  74. Li M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, Maruyama K, et al. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res. 2006;98(5):697–704.

    Article  Google Scholar 

  75. Jonas J, Witzens-Harig M, Arseniev L, Ho A. Intravitreal autologous bone marrow-derived mononuclear cell transplantation: a feasibility report. Acta Ophthalmol. 2008;86(2):225–6.

    Article  PubMed  Google Scholar 

  76. Siqueira R, Messias A, Voltarelli J, Scott I, Jorge R. Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina (Philadelphia, Pa). 2011;31(6):1207–14.

    Article  Google Scholar 

  77. Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao R. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun. 2005;332(2):370–9.

    Article  CAS  PubMed  Google Scholar 

  78. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove C, Bovenkerk J, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1292–8.

    Article  PubMed  Google Scholar 

  79. Traktuev D, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008;102(1):77–85.

    Article  CAS  PubMed  Google Scholar 

  80. Mendel T, Clabough E, Kao D, Demidova-Rice T, Durham J, Zotter B, et al. Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. Ljubimov A, editor. PLoS ONE Public Library of Science. 2013;8(5):e65691.

    Article  CAS  Google Scholar 

  81. Rajashekhar G, Ramadan A, Abburi C, Callaghan B, Traktuev D, Evans-Molina C, et al. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy. Chen J, editor. PLoS ONE Public Library of Science. 2014;9(1):e84671.

    Article  Google Scholar 

  82. MacLaren R, Pearson R, MacNeil A, Douglas R, Salt T, Akimoto M, et al. Retinal repair by transplantation of photoreceptor precursors. Nature. 2006;444(7116):203–7.

    Article  CAS  PubMed  Google Scholar 

  83. Pearson R, Barber A, Rizzi M, Hippert C, Xue T, West E, et al. Restoration of vision after transplantation of photoreceptors. Nature. 2012;485(7396):99–103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Barber A, Hippert C, Duran Y, West E, Bainbridge J, Warre-Cornish K, et al. Repair of the degenerate retina by photoreceptor transplantation. Proc Natl Acad Sci U S A. 2013;110(1):354–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Singh M, Issa P, Butler R, Martin C, Lipinski D, Sekaran S, et al. Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation. Proc Natl Acad Sci U S A. 2013;110(3):1101–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Gonzalez-Cordero A, West E, Pearson R, Duran Y, Carvalho L, Chu C, et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat Biotechnol. 2013;31(8):741–7.

    Article  CAS  PubMed  Google Scholar 

  87. Schwartz SD, Hubschman J, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713–20.

    Article  CAS  PubMed  Google Scholar 

  88. Simó R, Villarroel M, Corraliza L, Hernández C, Garcia-Ramírez M. The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier–implications for the pathogenesis of diabetic retinopathy. J Biomed Biotechnol. 2010;2010:190724.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Xu H, Le Y-Z. Significance of outer blood-retina barrier breakdown in diabetes and ischemia. Invest Ophthalmol Vis Sci. 2011;52(5):2160–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Gurdon J. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10:622–40.

    CAS  PubMed  Google Scholar 

  91. Wilmut I, Schnieke A, McWhir J, Kind A, Campbell K. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385(6619):810–3.

    Article  CAS  PubMed  Google Scholar 

  92. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    Article  CAS  PubMed  Google Scholar 

  93. Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8(5):409–12.

    Article  CAS  PubMed  Google Scholar 

  94. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011;472(7341):51–6.

    Article  CAS  PubMed  Google Scholar 

  95. Nakano T, Ando S, Takata N, Kawada M, Muguruma K, Sekiguchi K, et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell. 2012;10(6):771–85.

    Article  CAS  PubMed  Google Scholar 

  96. Phillips M, Perez E, Martin J, Reshel S, Wallace K, Capowski E, et al. Modeling human retinal development with patient-specific iPS cells reveals multiple roles for VSX2. Stem Cells. 2014;1–16. doi:10.1002/stem.1667.

  97. Kamao H, Mandai M, Okamoto S, Sakai N, Suga A, Sugita S, et al. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep. 2014;2(2):205–18.

    Article  CAS  Google Scholar 

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Roly Megaw and Bal Dhillon declare that they have no conflict of interest.

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Megaw, R., Dhillon, B. Stem Cell Therapies in the Management of Diabetic Retinopathy. Curr Diab Rep 14, 498 (2014). https://doi.org/10.1007/s11892-014-0498-9

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