Advertisement

Transplantation Immunology: Retinal Cell-Based Therapy

  • Harpal Sandhu
  • Janelle M. F. Adeniran
  • Henry J. Kaplan
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

The success of retinal cell-based therapy in regenerative medicine has many obstacles to overcome. One of the foremost barriers is acceptance of the retinal transplant in the subretinal space of the eye by the host’s immune system. Ocular immune privilege exists in several compartments of the eye including the subretinal space. However, immunologic privilege is a dynamic phenomenon that can be breached by the underlying disease and/or the host immune response. The success of retinal transplantation is not only dependent on the site of engraftment but also on the type of tissue/cell transplanted. The complex immunologic interaction between host, site of transplantation, and cell type transplanted will ultimately determine the potential of retinal cell-based therapy for the treatment of several retinal diseases. There is enormous promise for regenerative medicine to treat retinal diseases and preserve vision, but important issues still need to be resolved before translational clinical use.

Keywords

Immune privilege Alloantigen Transplantation Anterior chamber-associated immune deviation (ACAID) Immunologic tolerance Immunologic ignorance Graft rejection Innate immune response Adaptive immune response Subretinal space Immune suppression 

References

  1. 1.
    Medawar PB. Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948;29:58–69.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Billingham RE, Boswell T. Studies on the problem of corneal homografts. Proc R Soc Lond B Biol Sci. 1953;141:392–406.PubMedCrossRefGoogle Scholar
  3. 3.
    Kaplan HJ, Stevens TR. A reconsideration of immunological privilege within the anterior chamber of the eye. Transplantation. 1975;19:203–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kaplan HJ, Streilein JW. Immune response to immunization via the anterior chamber of the eye I. F1-lymphocyte-induced immune deviation. J Immunol. 1977;118:809–14.PubMedGoogle Scholar
  5. 5.
    Kaplan HJ, Streilein JW. Immune response to immunization via the anterior chamber of the eye II. An analysis of F1-lymphocyte-induced immune deviation. J Immunol. 1978;120:689–93.PubMedGoogle Scholar
  6. 6.
    Niederkorn JY. The role of the innate and adaptive immune responses in Acanthamoeba keratitis. Arch Immunol Ther Exp (Warsz). 2002a;50:53–9.Google Scholar
  7. 7.
    Niederkorn J, Streilein JW, Shadduck JA. Deviant immune responses to allogeneic tumors injected intracamerally and subcutaneously in mice. Invest Ophthalmol Vis Sci. 1981;20:355–63.PubMedGoogle Scholar
  8. 8.
    Niederkorn JY. Immune privilege in the anterior chamber of the eye. Crit Rev Immunol. 2002b;22:13–46.PubMedCrossRefGoogle Scholar
  9. 9.
    Niederkorn JY. Immunology and immunomodulation of corneal transplantation. Int Rev Immunol. 2002c;21:173–96.PubMedCrossRefGoogle Scholar
  10. 10.
    Streilein JW, Niederkorn JY, Shadduck JA. Systemic immune unresponsiveness induced in adult mice by anterior chamber presentation of minor histocompatibility antigens. J Exp Med. 1980;152:1121–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Streilein JW, Niederkorn JY. Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J Exp Med. 1981;153:1058–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Jiang LQ, Jorquera M, Streilein JW. Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci. 1993;34:3347–54.PubMedGoogle Scholar
  13. 13.
    Wenkel H, Chen PW, Ksander BR, Streilein JW. Immune privilege is extended, then withdrawn, from allogeneic tumor cell grafts placed in the subretinal space. Invest Ophthalmol Vis Sci. 1999;40:3202–8.PubMedGoogle Scholar
  14. 14.
    Ksander BR, Geer DC, Chen PW, et al. Uveal melanomas contain antigenically specific and non-specific infiltrating lymphocytes. Curr Eye Res. 1998;17:165–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Wilbanks GA, Streilein JW. Distinctive humoral immune responses following anterior chamber and intravenous administration of soluble antigen. Evidence for active suppression of IgG2-secreting B lymphocytes. Immunology. 1990;71:566–72.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Boonman ZF, van Mierlo GJ, Fransen MF, et al. Intraocular tumor antigen drains specifically to submandibular lymph nodes, resulting in an abortive cytotoxic T cell reaction. J Immunol. 2004;172:1567–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Camelo S, Kezic J, Shanley A, et al. Antigen from the anterior chamber of the eye travels in a soluble form to secondary lymphoid organs via lymphatic and vascular routes. Invest Ophthalmol Vis Sci. 2006;47:1039–46.PubMedCrossRefGoogle Scholar
  18. 18.
    Camelo S, Shanley A, Voon AS, et al. The distribution of antigen in lymphoid tissues following its injection into the anterior chamber of the rat eye. J Immunol. 2004;172:5388–95.PubMedCrossRefGoogle Scholar
  19. 19.
    Egan RM, Yorkey C, Black R, et al. Peptide-specific T cell clonal expansion in vivo following immunization in the eye, an immune-privileged site. J Immunol. 1996;157:2262–71.PubMedGoogle Scholar
  20. 20.
    Junghans BM, Wadley RB, Crewther SG, et al. X-ray elemental analysis differentiates blood vessels and lymphatic vessels in the chick choroid. Aust NZ J Ophthalmol. 1999;27:244–6.CrossRefGoogle Scholar
  21. 21.
    Liang H, Crewther SG, Crewther DP, et al. Structural and elemental evidence for edema in the retina, retinal pigment epithelium, and choroid during recovery from experimentally induced myopia. Invest Ophthalmol Vis Sci. 2004;45:2463–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Liu Y, Hamrah P, Zhang Q, et al. Draining lymph nodes of corneal transplant hosts exhibit evidence for donor major histocompatibility complex (MHC) class II-positive dendritic cells derived from MHC class II-negative grafts. J Exp Med. 2002;195:259–68.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Niederkorn JY, Lynch MG. Reconsidering the immunologic privilege and lymphatic drainage of the anterior chamber of the eye. Transplant Proc. 1989;21:259–60.PubMedGoogle Scholar
  24. 24.
    Niederkorn JY, Streilein JW. Alloantigens placed into the anterior chamber of the eye induce specific suppression of delayed-type hypersensitivity but normal cytotoxic T lymphocyte and helper T lymphocyte responses. J Immunol. 1983;131:2670–4.PubMedGoogle Scholar
  25. 25.
    Niederkorn JY, Kaplan HJ. Immune response and the eye. 2nd Revised ed. Basel: Karger; 2007.CrossRefGoogle Scholar
  26. 26.
    Taylor AW. Ocular immune privilege and transplantation. Front Immunol. 2016;7:37.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Xu H, Chen M. Targeting the complement system for the management of retinal inflammatory and degenerative diseases. Eur J Immunol. 2016;787:94–104.Google Scholar
  28. 28.
    McBride BW, McGill JI, Smith JL. MHC class I and class II antigen expression in normal human corneas and in corneas from cases of herpetic keratitis. Immunology. 1988;65(4):583–7.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Abi-Hanna D, Wakefield D, Watkins S. HLA antigens in ocular tissues. I. In vivo expression in human eyes. Transplantation. 1988;45:610–3.PubMedCrossRefGoogle Scholar
  30. 30.
    Cursiefen C, Chen L, Dana MR, et al. Corneal lymphangiogenesis: evidence, mechanisms, and implications for corneal transplant immunology. Cornea. 2003;22:273–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Hamrah P, Liu Y, Zhang O, et al. The corneal stroma is endowed with a significant number of resident dendritic cells. Invest Ophthalmol Vis Sci. 2003;44:581–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Lee RS, Grusby MJ, Glimcher LH, et al. Indirect recognition by helper cells can induce donor-specific cytotoxic T lymphocytes in vivo. J Exp Med. 1994;179:865–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Shoskes DA, Wood KJ. Indirect presentation of MHC antigens in transplantation. Immunol Today. 1994;15:32–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Streilein JW, Toews GB, Bergstresser PR. Corneal allografts fail to express Ia antigens. Nature. 1979;282:326–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Wang HM, Kaplan HJ, Chan WC, et al. The distribution and ontogeny of MHC antigens in murine ocular tissue. Invest Ophthalmol Vis Sci. 1987;28:1383–9.PubMedGoogle Scholar
  36. 36.
    Streilein JW. Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol. 2003;74:179–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Forrester JV, Xu H. Good news-bad news: the Yin and Yang of immune privilege in the eye. Front Immunol. 2012;3:338.  https://doi.org/10.3389/fimmu.2012.00338.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Chen X, Kezic J, Bernard C, et al. Rd8 mutation in the Crb1 gene of CD11c-eYFP transgenic reporter mice results in abnormal numbers of CD11c-positive cells in the retina. J Neuropathol Exp Neurol. 2013;72:782–90.PubMedCrossRefGoogle Scholar
  39. 39.
    Gregerson DS, Yang J. CD45-positive cells of the retina and their responsiveness to in vivo and in vitro treatment with IFN-gamma or anti-CD40. Invest Ophthalmol Vis Sci. 2003;44:3083–93.PubMedCrossRefGoogle Scholar
  40. 40.
    Karlstetter M, Scholz R, Rutar M. Retinal microglia: just bystander or target for therapy? Prog Retin Eye Res. 2015;45:30–57.PubMedCrossRefGoogle Scholar
  41. 41.
    Goslings WR, Prodeus AP, Streilein JW, et al. A small molecular weight factor in aqueous humor acts on C1q to prevent antibody-dependent complement activation. Invest Ophthalmol Vis Sci. 1998;39:989–95.PubMedGoogle Scholar
  42. 42.
    Sohn JH, Bora PS, Suk HJ, et al. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat Med. 2003;9:206–12.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Anderson DH, Radeke MJ, Gallo NB, et al. The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res. 2010;29:95–112.PubMedCrossRefGoogle Scholar
  44. 44.
    Luo C, Chen M, Xu H. Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid. Mol Vis. 2011;17:1588–97.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Bora NS, Gobleman CL, Atkinson JP, et al. Differential expression of the complement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci. 1993;34:3579–84.PubMedGoogle Scholar
  46. 46.
    Jha P, Sohn JH, Xu Q, et al. The complement system plays a critical role in the development of experimental autoimmune anterior uveitis. Invest Ophthalmol Vis Sci. 2006;47:1030–8.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Lass JH, Walter EI, Burris TE, et al. Expression of two molecular forms of the complement decay-accelerating factor in the eye and lacrimal gland. Invest Ophthalmol Vis Sci. 1990;31:1136–48.PubMedGoogle Scholar
  48. 48.
    Lee HO, Herndon JM, Barreiro R, et al. TRAIL: a mechanism of tumor surveillance in an immune privileged site. J Immunol. 2002;169:4739–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Sohn JH, Kaplan HJ, Suk HJ, et al. Complement regulatory activity of normal human intraocular fluid is mediated by MCP, DAF, and CD59. Invest Ophthalmol Vis Sci. 2000a;41:4195–202.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Sohn JH, Kaplan HJ, Suk HJ, et al. Chronic low-level complement activation within the eye is controlled by intraocular complement regulatory proteins. Invest Ophthalmol Vis Sci. 2000b;41:3492–502.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Wang S, Boonman ZF, Li HC, et al. Role of TRAIL and IFN-gamma in CD4+ T cell-dependent tumor rejection in the anterior chamber of the eye. J Immunol. 2003;171:2789–96.PubMedCrossRefGoogle Scholar
  52. 52.
    Yoshida M, Takeuchi M, Streilein JW. Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact. Invest Ophthalmol Vis Sci. 2000;41:811–21.PubMedGoogle Scholar
  53. 53.
    Amadi-Obi A, Yu CR, Dambuza I, et al. Interleukin 27 induces the expression of complement factor H (CFH) in the retina. PLoS One. 2012;7:e45801.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Lau LI, Chiou SH, Liu CJ, et al. The effect of photo-oxidative stress and inflammatory cytokine on complement factor H expression in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2011;52:6832–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Luo C, Zhao J, Madden A, et al. Complement expression in retinal pigment epithelial cells is modulated by activated macrophages. Exp Eye Res. 2013;112C:93–101.CrossRefGoogle Scholar
  56. 56.
    Jiang LQ, Streilein JW. Immune privilege extended to allogeneic tumor cells in the vitreous cavity. Invest Ophthalmol Vis Sci. 1991a;32:224–8.PubMedGoogle Scholar
  57. 57.
    Wenkel H, Streilein JW. Analysis of immune deviation elicited by antigens injected into the subretinal space. Invest Ophthalmol Vis Sci. 1998;39:1823–34.PubMedGoogle Scholar
  58. 58.
    Xian B, Huang B. The immune response of stem cells in subretinal transplantation. Stem Cell Res Ther 2015;6:161 doi: 10.1186/s13287-015-0167-1.Google Scholar
  59. 59.
    Schrodl F, Kaser-Eichberger A, Trost A, et al. Lymphatic markers in the adult human choroid. Invest Ophthalmol Vis Sci. 2015;56:7406–16.Google Scholar
  60. 60.
    Schrodl F, Kaser-Eichberger A, Schlereth SL, et al. Consensus statement on the immunohistochemical detection of ocular lymphatic vessels. Invest Ophthalmol Vis Sci. 2014;55:6440–2.CrossRefGoogle Scholar
  61. 61.
    Mo JS, Streilein JW. Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS. Eur J Immunol. 2001;31:3806–15.PubMedCrossRefGoogle Scholar
  62. 62.
    Ohta K, Wiggert B, Yamagami S, et al. Analysis of immunomodulatory activities of aqueous humor from eyes of mice with experimental autoimmune uveitis. J Immunol. 2000a;164:1185–92.PubMedCrossRefGoogle Scholar
  63. 63.
    Ohta K, Yamagami S, Taylor AW, et al. Il-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci. 2000b;41:2591–9.PubMedGoogle Scholar
  64. 64.
    Streilein JW, Ohta K, Mo JS, et al. Ocular immune privilege and the impact of intraocular inflammation. DNA Cell Biol. 2002a;21:453–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Davidson A, Fairchild R, Holmdahl R, et al. In: Janeway’s Immunol, editor. Autoimmunity and transplantation. 9th ed. New York: Garland Science, Taylor and Francis Group; 2017. p. 643–94.Google Scholar
  66. 66.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.CrossRefPubMedGoogle Scholar
  68. 68.
    Solomon S, Pitossi F, Rao MS. Banking on iPSC—is it doable and is it worthwhile. Stem Cell Rev. 2015;11:1–10.PubMedCrossRefGoogle Scholar
  69. 69.
    Opelz G, Dohler B. Association of HLA a mismatch with death with a functioning graft after kidney transplantation: a collaborative transplant study report. Am J Transplant. 2012;12:3031–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Susal C, Opelz G. Current role of human leukocyte antigen matching in kidney transplantation. Curr Opin Organ Transplant. 2013;18:438–44.PubMedCrossRefGoogle Scholar
  71. 71.
    Sugita S, Iwasaki Y, Makabe K, et al. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-Matched Models. Stem Cell Reports 2016;7(4):635-48 doi: 10.1016/j.stemcr.2016.08.010.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Bilbao I, Dopazo C, Castells L, et al. Immunosuppression based on everolimus in liver transplant recipients with severe early post-transplantation neurotoxicity. Transplant Proc. 2014;46:3104–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Hart M, Thakral B, Yohe S, et al. EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent post transplant lymphoproliferative disorder. Am J Surg Pathol. 2014;38:1522–9.Google Scholar
  74. 74.
    Meaney CJ, Arabi Z, Venuto RC, et al. Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients. BMC Nephrol. 2014;15:88.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Santos L, Rodrigo E, Pinera C, et al. New-onset diabetes after transplantation: drug-related risk factors. Transplant Proc. 2012;44:2585–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Wu C, Shapiro R. Post-transplant malignancy: reducing the risk in kidney transplant recipients. Expert Opin Pharmacother. 2011;12:1719–29.PubMedCrossRefGoogle Scholar
  77. 77.
    Figueiredo C, Blascyzk R. A future with less HLA: potential clinical applications of HLA-universal cells. Tissue Antigens. 2015;85:443–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Zhao T, Zhang Z, Westenskow PD, et al. Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell. 2015;17:353–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Drukker M, Katz G, Urbach A, et al. Characterization of the expression of MHC proteins in human embryonic stem cells. Proc Natl Acad Sci. 2002;99:9864–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Drukker M, Katchman H, Katz G, et al. Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells. 2006;24:221–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Li L, Baroja ML, Majumdar A, et al. Human embryonic stem cells possess immune-privileged properties. Stem Cells. 2004;22:448–56.PubMedCrossRefGoogle Scholar
  82. 82.
    Menard C, Hagege AA, Agbulut O, et al. Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a pre-clinical study. Lancet. 2005;366:1005–12.PubMedCrossRefGoogle Scholar
  83. 83.
    Suarez-Alvarez B, Rodriguez RM, Calvanese V, et al. Epigenetic mechanisms regulate MHC and antigen processing molecules in human embryonic and induced pluripotent stem cells. PLoS One. 2010;5:e10192.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Swijnenburg RJ, Tanaka M, Vogel H, et al. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation. 2005;112:166–72.Google Scholar
  85. 85.
    Robertson NJ, Brook FA, Gardner RL, et al. Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance. Proc Natl Acad Sci U S A. 2007;104:20920–5.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Yachimovich-Cohen N, Even-Ram S, Shufaro Y, et al. Human embryonic stem cells suppress T cell responses via arginase I-dependent mechanism. J Immunol. 2010;184:1300–8.PubMedCrossRefGoogle Scholar
  87. 87.
    Yen BL, Chang CJ, Liu KJ, et al. Brief report-human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward nature killer cells as well as T lymphocytes. Stem Cells. 2009;27:451–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Foldes G, Liu A, Badiger R, et al. Innate immunity in human embryonic stem cells: comparison with adult human endothelial cells. PLoS One. 2010;5:e10501.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Chidgey AP, Boyd RL. Immune privilege for stem cells: not as simple as it looked. Cell Stem Cell. 2008;3:357–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Hall BM, Dorsch S, Roser B. The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts. J Exp Med. 1978;148:878–89.PubMedCrossRefGoogle Scholar
  91. 91.
    Swijnenburg RJ, Schrepfer S, Govaert JA, et al. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc Natl Acad Sci. 2008;105:12991–6.PubMedCrossRefGoogle Scholar
  92. 92.
    Wu DC, Boyd AS, Wood KJ. Embryonic stem cells and their differentiated derivatives have a fragile immune privilege but still represent novel targets of immune attack. Stem Cells. 2008;26:1939–50.PubMedCrossRefGoogle Scholar
  93. 93.
    Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95:379–91.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Rong Z, Wang M, Zhen H, et al. An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell. 2014;14:121–30.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Zhu J, Cifuentes JR, Reynolds J. Immunosuppression via loss of IL2rγ enhances long-term functional integration of hESC-derived photoreceptors in the mouse retina. Cell Stem Cell. 2017;20:374–84.PubMedCrossRefGoogle Scholar
  96. 96.
    West EL, Pearson RA, Barker SE, et al. Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation. Stem Cells. 2010;28:1997–2007.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Ishioka M, Okamoto S, Streilein JW, Jiang LQ. Effect of cyclosporine on anterior chamber-associated immune deviation with retinal transplantation. Invest Ophthalmol Vis Sci 1997;38(10):2152-60.Google Scholar
  98. 98.
    Pearson RA, Gonzalez-Cordero A, El W. Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors. Nat Commun. 2016;7:13029.  https://doi.org/10.1038/ncomms13029.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Santos-Ferreira T, Llonch S, Borsch O, et al. Retinal transplantation of photoreceptors results in donor-host cytoplasmic exchange. Nat Commun. 2016;7:13028.  https://doi.org/10.1038/ncomms13028.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    MacLaren RE, Pearson RA, MacNeil A, et al. Retina repair by transplantation of photoreceptor precursors. Nature. 2006;444:203–7.Google Scholar
  101. 101.
    Zhou L, Wang W, Liu Y, et al. Differentiation of induced pluripotent stem cells of swine into rod photoreceptors and their integration into the retina. Stem Cells. 2011;29:972–80.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Garside P, Millington O, Smith KM. The anatomy of mucosal immune responses. Ann N Y Acad Sci. 2004;1029:9–15.PubMedCrossRefGoogle Scholar
  103. 103.
    Jiang LQ, Jorquera M, Streilein JW. Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res. 1994;58:719–28.PubMedCrossRefGoogle Scholar
  104. 104.
    Dubois B, Goubier A, Joubert G, et al. Oral tolerance and regulation of mucosal immunity. Cell Mol Life Sci. 2005;62:1322–32.PubMedCrossRefGoogle Scholar
  105. 105.
    Jiang LQ, Streilein JW. Immune responses elicited by transplantation and tissue-restricted antigens expressed on retinal tissues implanted subconjunctivally. Transplantation. 1991b;53:513–9.CrossRefGoogle Scholar
  106. 106.
    Jiang LQ, Streilein JW. Immunity and immune privilege elicited by autoantigens expressed on syngeneic neonatal neural retina grafts. Curr Eye Res. 1992;11:697–709.PubMedCrossRefGoogle Scholar
  107. 107.
    Choi C, Benveniste EN. Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses. Brain Res Brain Res Rev. 2004;44:65–81.PubMedCrossRefGoogle Scholar
  108. 108.
    Griffith TS, Brunner T, Fletcher SM, et al. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270:1189–92.PubMedCrossRefGoogle Scholar
  109. 109.
    Sata M, Suhara T, Walsh K. Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas ligand-induced cell death: implications for vascular disease and therapy. Arterioscler Thromb Vasc Biol. 2000;20:309–16.PubMedCrossRefGoogle Scholar
  110. 110.
    Walsh K, Sata M. Is extravasation a Fas-regulated process? Mol Med Today. 1999;5:61–7.PubMedCrossRefGoogle Scholar
  111. 111.
    Harling-Berg C, Knopt PM, Merriam J, et al. Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid. J Neuroimmunol. 1989;25:185–93.PubMedCrossRefGoogle Scholar
  112. 112.
    Mishra A, Das B, Nath M, et al. A novel immunodeficient NOD.SCID-rd1 mouse model of retinitis pigmentosa to investigate potential therapeutics and pathogenesis of retinal degeneration. Biol Open. 2017;6:449–62.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Gullapalli VK, Khodair MA, Wang H, et al. Transplantation frontiers. In: Ryan SJ, editor. Retina, vol. 3. 5th ed. Philadelphia, PA: Mosby, Inc.; 2013. p. 2058–77.CrossRefGoogle Scholar
  114. 114.
    Zarbin M. Cell-based therapy for degenerative retinal disease. Trends Mol Med. 2016;22:115–34.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Algvere PV, Berglin L, Gouras P, et al. Transplantation of RPE in age-related macular degeneration: observations in disciform lesions and dry RPE atrophy. Graefes Arch Clin Exp Ophthalmol. 1997;235:149–58.PubMedCrossRefGoogle Scholar
  116. 116.
    Algvere PV, Gouras P, Dafgard KE. Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD. Eur J Ophthalmol. 1999;9:217–30.PubMedCrossRefGoogle Scholar
  117. 117.
    Tezel TH, Del Priore LV, Berger AS, et al. Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am J Ophthalmol. 2007;143:584–95.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Del Priore LV, Ishida O, Johnson EW, et al. Triple immune suppression increases short-term survival of porcine fetal retinal pigment epithelium xenografts. Invest Ophthalmol Vis Sci. 2003;44:4044–53.PubMedCrossRefGoogle Scholar
  119. 119.
    Del Priore LV, Tezel TH, Kaplan HJ. Survival of allogeneic porcine retinal pigment epithelial sheets after subretinal transplantation. Invest Ophthalmol Vis Sci. 2004;45:985–92.CrossRefPubMedGoogle Scholar
  120. 120.
    Streilein JW, Ma N, Wenkel H, et al. Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Res. 2002b;42:487–95.PubMedCrossRefGoogle Scholar
  121. 121.
    Ye J, Wang HM, Odgen TE, et al. Allotransplantation of rabbit retinal pigment epithelial cells double-labeled with 5-bromodeoxyuridine (BrdU) and natural pigment. Curr Eye Res. 1993;12:629–39.PubMedCrossRefGoogle Scholar
  122. 122.
    Binder S, Krebs I, Hilgers RD, et al. Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci. 2004;45:4151–60.PubMedCrossRefGoogle Scholar
  123. 123.
    Falkner-Radler CJ, Krebs I, Glittenberg C, et al. Human retinal pigment epithelium transplantation: outcome after autologous RPE-choroid sheet and RPE cell suspension in a randomized clinical study. Br J Ophthalmol. 2011;95:370–5.PubMedCrossRefGoogle Scholar
  124. 124.
    MacLaren RE, Uppal GS, Balaggan KS, et al. Autologous translocation of the retinal pigment epithelium and choroid in treatment of neovascular age-related macular degeneration. Am J Ophthalmol. 2007;114:561–70.Google Scholar
  125. 125.
    Algvere PV, Berglin L, Gouras P, et al. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Exp Ophthalmol. 1994;232:707–16.CrossRefGoogle Scholar
  126. 126.
    Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase I/II studies. Lancet. 2015;385:509–16.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Schwartz SD, Tan G, Hosseini H, et al. Subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium for the treatment of macular degeneration: an assessment at 4 years. Invest Ophthalmol. 2016;57:ORSFc1–9.CrossRefGoogle Scholar
  128. 128.
    Da Cruz L, Dorn JD, Humayun MS, et al. Five-year safety and performance results from the Argus II retinal prosthesis system clinical trial. Ophthalmology. 2016;123:2248–54.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Humayun M, Propst R, de Juan E Jr, et al. Bipolar surface electrical stimulation of the vertebrate retina. Arch Ophthalmol. 1994;112:110–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Jones BW, Watt CB, Frederick JM, et al. Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol. 2003;464:1–16.PubMedCrossRefGoogle Scholar
  131. 131.
    Jones BW, Pfeiffer RL, Ferrell WD, et al. Retinal remodeling in human retinitis pigmentosa. Exp Eye Res. 2016;150:149–65.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Milam AH, Li ZY, Fariss RN. Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res. 1998;17:175–205.PubMedCrossRefGoogle Scholar
  133. 133.
    Berger AS, Tezel TH, Del Priore LV, et al. Photoreceptor transplantation in retinitis pigmentosa: short-term follow-up. Ophthalmology. 2003;110:383–91.PubMedCrossRefGoogle Scholar
  134. 134.
    Das T, del Cerro M, Jalali S, et al. The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study. Exp Neuro. 1999;157(1):58–68.CrossRefGoogle Scholar
  135. 135.
    Humayun MS, de Juan E Jr, Del Cerro M, et al. Human neural retinal transplantation. Invest Ophthalmol Vis Sci. 2000;41:3199–06.Google Scholar
  136. 136.
    Radtke ND, Seiler MJ, Aramant RB, et al. Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients. Am J Ophthalmol. 2002;133:544–50.PubMedCrossRefGoogle Scholar
  137. 137.
    Kaplan HJ, Tezel TH, Berger AS. Human photoreceptor transplantation in retinitis pigmentosa. Arch Ophthalmol. 1997;15:1168–72.CrossRefGoogle Scholar
  138. 138.
    Del Cerro M, Humayun MS, Sadda SR, et al. Histologic correlation of human neural retinal transplantation. Invest Ophthalmol Vis Sci. 2000;41:3142–8.PubMedGoogle Scholar
  139. 139.
    Gouras P, Du J, Gelanze M, et al. Survival and synapse formation of transplanted rat rods. J Neural Transplant Plast. 1991;2:91–100.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Del Cerro M, Ison JR, Bowen GP, et al. Intraretinal grafting restores visual function in light-blinded rats. Neuroreport. 1991;2:259–32.Google Scholar
  141. 141.
    English K, Wood KJ. Immunogenicity of embryonic stem cell-derived progenitors after transplantation. Curr Opin Organ Transplant. 2011;16:90–5.PubMedCrossRefGoogle Scholar
  142. 142.
    Ng TF, Osawa H, Hori J, et al. Allogeneic neonatal neuronal retina grafts display partial immune privilege in the subcapsular space of the kidney. J Immunol. 2002;169:5601–6.PubMedCrossRefGoogle Scholar
  143. 143.
    Radtke ND, Aramant RB, Heywood M, et al. Vision improvement in retinal degeneration patients by implantation of retina together with retinal pigment epithelium. Am J Ophthalmol. 2008;146:172–82.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Harpal Sandhu
    • 1
  • Janelle M. F. Adeniran
    • 1
  • Henry J. Kaplan
    • 1
  1. 1.Department of Ophthalmology and Visual SciencesUniversity of LouisvilleLouisvilleUSA

Personalised recommendations