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Stem Cells, Mechanism-Based Therapies and Regenerative Medicine Approaches

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Stem Cell Biology and Regenerative Medicine in Ophthalmology

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

The degeneration of photoreceptors and retinal pigment epithelium is the cause of many inherited and acquired ocular disorders that can lead to blindness. Some of these disorders are caused by single gene mutations while others are caused by polygenic mutations or environmental factors. In the past, animal models and gene therapy have aimed at correcting single gene mutations in diseased retina. But more recently, advances in stem cell research, together with advances in retinal tissue transplantation, have moved forward the possibility of treating patients with polygenic or environmental causes of retinal degeneration. Stem cells can now be derived from many sources, including peripheral blood, and successfully differentiated into retinal precursors. In addition, retinal tissue transplantation has been successfully demonstrated in both animals and humans. This article will review recent advances in the study and treatment of retinal disease.

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References

  1. D'Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9(4):645–651. doi:ddd061[pii]

    Article  PubMed  Google Scholar 

  2. Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U (2006) A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet 38(10):1173–1177, doi:ng1890[pii]10.1038/ng1890

    Article  PubMed  CAS  Google Scholar 

  3. Ennis S, Jomary C, Mullins R, Cree A, Chen X, Macleod A, Jones S, Collins A, Stone E, Lotery A (2008) Association between the SERPING1 gene and age-related macular degeneration: a two-stage case–control study. Lancet 372(9652):1828–1834. doi:S0140-6736(08)61348-3[pii]10.1016/S0140-6736(08)61348-3

    Article  PubMed  CAS  Google Scholar 

  4. Schmidt S, Hauser MA, Scott WK, Postel EA, Agarwal A, Gallins P, Wong F, Chen YS, Spencer K, Schnetz-Boutaud N, Haines JL, Pericak-Vance MA (2006) Cigarette smoking strongly modifies the association of LOC387715 and age-related macular degeneration. Am J Hum Genet 78(5):852–864. doi:S0002-9297(07)63818-X[pii]10.1086/503822

    Article  PubMed  CAS  Google Scholar 

  5. Kanda A, Chen W, Othman M, Branham KE, Brooks M, Khanna R, He S, Lyons R, Abecasis GR, Swaroop A (2007) A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci USA 104(41):16227–16232. doi:0703933104[pii]10.1073/pnas.0703933104

    Article  PubMed  CAS  Google Scholar 

  6. Allikmets R (1997) A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 17(1):122. doi:10.1038/ng0997-122a

    PubMed  CAS  Google Scholar 

  7. Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, Gerrard B, Baird L, Stauffer D, Peiffer A, Rattner A, Smallwood P, Li Y, Anderson KL, Lewis RA, Nathans J, Leppert M, Dean M, Lupski JR (1997) A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 15(3):236–246. doi:10.1038/ng0397-236

    Article  PubMed  CAS  Google Scholar 

  8. Sparrow JR, Boulton M (2005) RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 80(5):595–606. doi:S0014-4835(05)00019-9[pii]10.1016/j.exer.2005.01.007

    Article  PubMed  CAS  Google Scholar 

  9. Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH (1999) Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell 98(1):13–23. doi:S0092-8674(00)80602-9[pii]10.1016/S0092-8674(00)80602-9

    Article  PubMed  CAS  Google Scholar 

  10. Kong J, Kim SR, Binley K, Pata I, Doi K, Mannik J, Zernant-Rajang J, Kan O, Iqball S, Naylor S, Sparrow JR, Gouras P, Allikmets R (2008) Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy. Gene Ther 15(19):1311–1320. doi:gt200878[pii]10.1038/gt.2008.78

    Article  PubMed  CAS  Google Scholar 

  11. Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28(1):92–95. doi:10.1038/8832788327[pii]

    PubMed  CAS  Google Scholar 

  12. Cideciyan AV (2010) Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res 29(5):398–427. doi:S1350-9462(10)00028-5[pii]10.1016/j.preteyeres.2010.04.002

    Google Scholar 

  13. Haruta M, Sasai Y, Kawasaki H, Amemiya K, Ooto S, Kitada M, Suemori H, Nakatsuji N, Ide C, Honda Y, Takahashi M (2004) In vitro and in vivo characterization of pigment epithelial cells differentiated from primate embryonic stem cells. Invest Ophthalmol Vis Sci 45(3):1020–1025

    Article  PubMed  Google Scholar 

  14. 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. Proc Natl Acad Sci USA 102(32):11331–11336. doi:0500010102[pii]10.1073/pnas.0500010102

    Article  PubMed  CAS  Google Scholar 

  15. Banin E, Obolensky A, Idelson M, Hemo I, Reinhardtz E, Pikarsky E, Ben-Hur T, Reubinoff B (2006) Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells 24(2):246–257. doi:2005-0009[pii]10.1634/stemcells.2005-0009

    Article  PubMed  Google Scholar 

  16. Lamba DA, Karl MO, Ware CB, Reh TA (2006) Efficient generation of retinal progenitor cells from human embryonic stem cells. Proc Natl Acad Sci USA 103(34):12769–12774. doi:0601990103[pii]10.1073/pnas.0601990103

    Article  PubMed  CAS  Google Scholar 

  17. Vugler A, Carr AJ, Lawrence J, Chen LL, Burrell K, Wright A, Lundh P, Semo M, Ahmado A, Gias C, da Cruz L, Moore H, Andrews P, Walsh J, Coffey P (2008) Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation. Exp Neurol 214(2):347–361. doi:S0014-4886(08)00358-0[pii]10.1016/j.expneurol.2008.09.007

    Article  PubMed  CAS  Google Scholar 

  18. Carr AJ, Vugler A, Lawrence J, Chen LL, Ahmado A, Chen FK, Semo M, Gias C, da Cruz L, Moore HD, Walsh J, Coffey PJ (2009) Molecular characterization and functional analysis of phagocytosis by human embryonic stem cell-derived RPE cells using a novel human retinal assay. Mol Vis 15:283–295

    PubMed  CAS  Google Scholar 

  19. Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, Akaike A, Sasai Y, Takahashi M (2008) Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol 26(2):215–224. doi:nbt1384[pii]10.1038/nbt1384

    Article  PubMed  CAS  Google Scholar 

  20. Yamanaka S (2010) Patient-specific pluripotent stem cells become even more accessible. Cell Stem Cell 7(1):1–2. doi:S1934-5909(10)00291-2[pii]10.1016/j.stem.2010.06.009

    Article  PubMed  CAS  Google Scholar 

  21. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:S0092-8674(06)00976-7[pii]10.1016/j.cell.2006.07.024

    Article  PubMed  CAS  Google Scholar 

  22. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:S0092-8674(07)01471-7[pii]10.1016/j.cell.2007.11.019

    Article  PubMed  CAS  Google Scholar 

  23. Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R (2010) Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell 7(1):20–24. doi:S1934-5909(10)00284-5[pii]10.1016/j.stem.2010.06.002

    Article  PubMed  CAS  Google Scholar 

  24. Loh YH, Hartung O, Li H, Guo C, Sahalie JM, Manos PD, Urbach A, Heffner GC, Grskovic M, Vigneault F, Lensch MW, Park IH, Agarwal S, Church GM, Collins JJ, Irion S, Daley GQ (2010) Reprogramming of T cells from human peripheral blood. Cell Stem Cell 7(1):15–19. doi:S1934-5909(10)00286-9[pii]10.1016/j.stem.2010.06.004

    Article  PubMed  Google Scholar 

  25. Seki T, Yuasa S, Oda M, Egashira T, Yae K, Kusumoto D, Nakata H, Tohyama S, Hashimoto H, Kodaira M, Okada Y, Seimiya H, Fusaki N, Hasegawa M, Fukuda K (2010) Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7(1):11–14. doi:S1934-5909(10)00285-7[pii]10.1016/j.stem.2010.06.003

    Article  PubMed  CAS  Google Scholar 

  26. 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. Neurosci Lett 458(3):126–131. doi:S0304-3940(09)00502-3[pii]10.1016/j.neulet.2009.04.035

    Article  PubMed  CAS  Google Scholar 

  27. Gouras P, Kong J, Tsang SH (2002) Retinal degeneration and RPE transplantation in Rpe65(−/−) mice. Invest Ophthalmol Vis Sci 43(10):3307–3311

    PubMed  Google Scholar 

  28. Kaplan HJ, Tezel TH, Berger AS, Del Priore LV (1999) Retinal transplantation. Chem Immunol 73:207–219

    Article  PubMed  CAS  Google Scholar 

  29. Radtke ND, Seiler MJ, Aramant RB, Petry HM, Pidwell DJ (2002) Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients. Am J Ophthalmol 133(4):544–550. doi:S0002939402013223[pii]

    Article  PubMed  Google Scholar 

  30. Algvere PV, Berglin L, Gouras P, Sheng Y (1994) Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol 232(12):707–716

    Article  PubMed  CAS  Google Scholar 

  31. Algvere PV, Berglin L, Gouras P, Sheng Y, Kopp ED (1997) Transplantation of RPE in age-related macular degeneration: observations in disciform lesions and dry RPE atrophy. Graefes Arch Clin Exp Ophthalmol 235(3):149–158

    Article  PubMed  CAS  Google Scholar 

  32. Algvere PV, Gouras P, Dafgard Kopp E (1999) Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol 9(3):217–230

    PubMed  CAS  Google Scholar 

  33. Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B, Girman S, Bischoff N, Sauve Y, Lanza R (2006) Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats. Cloning Stem Cells 8(3):189–199. doi:10.1089/clo.2006.8.189

    Article  PubMed  CAS  Google Scholar 

  34. Sauve Y, Pinilla I, Lund RD (2006) Partial preservation of rod and cone ERG function following subretinal injection of ARPE-19 cells in RCS rats. Vision Res 46(8–9):1459–1472. doi:S0042-6989(05)00585-7[pii]10.1016/j.visres.2005.11.009

    Article  PubMed  CAS  Google Scholar 

  35. Wang S, Lu B, Girman S, Holmes T, Bischoff N, Lund RD (2008) Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration. Invest Ophthalmol Vis Sci 49(1):416–421. doi:49/1/416[pii]10.1167/iovs.07-0992

    Article  PubMed  Google Scholar 

  36. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5(4):396–408. doi:S1934-5909(09)00336-1[pii]10.1016/j.stem.2009.07.002

    Article  PubMed  CAS  Google Scholar 

  37. MacLaren RE, Uppal GS, Balaggan KS, Tufail A, Munro PM, Milliken AB, Ali RR, Rubin GS, Aylward GW, da Cruz L (2007) Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration. Ophthalmology 114(3):561–570. doi:S0161-6420(06)01057-8[pii]10.1016/j.ophtha.2006.06.049

    Article  PubMed  Google Scholar 

  38. Lamba DA, Gust J, Reh TA (2009) Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4(1):73–79. doi:S1934-5909(08)00538-9[pii]10.1016/j.stem.2008.10.015

    Article  PubMed  CAS  Google Scholar 

  39. Joussen AM, Joeres S, Fawzy N, Heussen FM, Llacer H, van Meurs JC, Kirchhof B (2007) Autologous translocation of the choroid and retinal pigment epithelium in patients with geographic atrophy. Ophthalmology 114(3):551–560. doi:S0161-6420(06)01133-X[pii]10.1016/j.ophtha.2006.08.016

    Article  PubMed  Google Scholar 

  40. van Zeeburg EJ, Maaijwee KJ, Missotten TO, Heimann H, van Meurs JC (2012) A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years. Am J Ophthalmol 153 (1):120–127 e122. doi:S0002-9394(11)00478-8[pii]10.1016/j.ajo.2011.06.007

    Google Scholar 

  41. Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379:713–720. doi:S0140-6736(12)60028-2[pii]10.1016/S0140-6736(12)60028-2

    Google Scholar 

  42. Mellough CB, Steel DH, Lako M (2009) Genetic basis of inherited macular dystrophies and implications for stem cell therapy. Stem Cells 27(11):2833–2845. doi:10.1002/stem.159

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Ophthalmology, Columbia University, New York, NY, USA

    Xining He & Deniz Erol

  2. Yale Eye Center, Yale University, New Haven, CT, USA

    Xining He

  3. Department of Ophthalmology & Department of Pathology & Cell Biology, Columbia University, New York, NY, USA

    Stephen H. Tsang

  4. Columbia Stem Cell Initiative, Columbia University Medical Center, New York, NY, USA

    Stephen H. Tsang

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  1. Xining He
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  2. Deniz Erol
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  3. Stephen H. Tsang
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Correspondence to Xining He .

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Editors and Affiliations

  1. Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University, 160 Fort Washington Avenue, Room 513, New York, 10032, New York, USA

    Stephen H. Tsang

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He, X., Erol, D., Tsang, S.H. (2013). Stem Cells, Mechanism-Based Therapies and Regenerative Medicine Approaches. In: Tsang, S. (eds) Stem Cell Biology and Regenerative Medicine in Ophthalmology. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5493-9_7

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