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Tolerance of human fetal retinal pigment epithelium xenografts in monkey retina

  • Lennart Berglin
  • Peter Gouras
  • Yoahua Sheng
  • Javier Lavid
  • Po-Kang Lin
  • Huiyun Cao
  • Hild Kjeldbye
Laboratory Investigation

Abstract

• Background: RPE transplantation offers the possibility of treating certain forms of retinal degeneration. Understanding how to optimize the surgical technique for performing RPE transplantation, especially in primates, is therefore of considerable interest. • Methods: Fifteen patch RPE transplants were performed in six monkeys. The transplant sites were examined at follow-up by ophthalmoscopy, biomicroscopy, fluorescein angiography and histology. Foveal and peripheral retinal transplants were compared. • Results: Human fetal RPE xenografts can survive without rejection for at least 6 months after transplantation in monkey retina. Such grafts form a basal lamina and make intimate contacts with the outer segments of the host. Both rods and cones retain a normal appearance when in contact with unrejected transplants. Rejection occurred in only 30% (3/10) of the peripheral but in 60% (3/5) of the foveal transplants. • Conclusions: Cultured human fetal RPE patch transplants can survive and maintain local photoreceptor integrity for relatively long periods of time in monkey subretinal space without immunosuppression. Rejection, when it occurs, is more frequent near the fovea.

Keywords

Retina Fluorescein Retinal Pigment Epithelium Basal Lamina Retinal Pigment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Algvere PV, Berglin L, Gouras P, Sheng Y (1994) Transplantation of fetal retinal pigment epithelium in agerelated macular degeneration with subfoveal neovascularization. Graefe's Arch Clin Exp Ophthalmol 232:707–716Google Scholar
  2. 2.
    Algvere P, Berglin L, Gouras P, Sheng Y (1996) Human fetal RPE transplants in age-related macular degeneration. Invest Ophthalmol Vis Sci 37: 596Google Scholar
  3. 3.
    Anderson DH, Stern WH, Fisher SK, Erickson PA, Borgula GA (1983) Retinal detachment in the cat: the pigment epithelial-photoreceptor interface. Invest Ophthalmol Vis Sci 24:906–926Google Scholar
  4. 4.
    Cook B, Lewis GP, Fisher SK, Adler R (1995) Apoptotic photoreceptor degeneration in experimental retinal detachment. Invest Ophthalmol Vis Sci 36:990–996Google Scholar
  5. 5.
    deVos AF, Klaren VNA, Kijlstra A (1994) Expression of multiple cytokines and IL-IRA in the uvea and retina during endotoxin-induced uveitis in the rat. Invest Ophthalmol Vis Sci 35:3873–3883Google Scholar
  6. 6.
    El Dirini AA, Wang H, Ogden TE, Ryan SJ (1992) Retinal pigment epithelium implantation in the rabbit: technique and morphology. Graefe's Arch Clin Exp Ophthalmol 230:292–300Google Scholar
  7. 7.
    Erickson PA, Fisher SK, Anderson DH, Stern WH, Borgula GA (1983) Retinal detachment in the cat: the outer nuclear and outer plexiform layers. Invest Ophthalmol Vis Sci 24: 927–942Google Scholar
  8. 8.
    Foulds WS (1963) Experimental retinal detachment. Trans Ophthalmol Soc UK 83:153–159Google Scholar
  9. 9.
    Fraunfelder FT, Potts AM (1966) An experimental study of retinal detachments. Am J Ophthalmol 62:561–567Google Scholar
  10. 10.
    Gouras P, Cao H, Sheng Y, Tanabe T, Effremova Y, Kjeldbye H (1994) Patch culturing and transfer of human fetal retinal epithelium. Graefe's Arch Clin Exp Ophthalmol 232: 599–607Google Scholar
  11. 11.
    Gouras P, Du J, Kjeldbye H, Yamamoto S, Zack DJ (1994) Long-term photoreceptor transplants in dystrophic and normal mouse retina. Invest Ophthalmol Vis Sci 35: 3145–3153Google Scholar
  12. 12.
    Gouras P, Berglin L, Sheng Y, et al (1995) Long term human RPE transplants in monkey retina. Invest Ophthalmol Vis Sci 36[Suppl]:S211Google Scholar
  13. 13.
    Head JR, Griffin WS (1985) Functional capacity of solid tissue transplants in the brain: evidence for immunological privilege. Proc R Soc Lond (Biol) 224:375–387Google Scholar
  14. 14.
    Isuno M, Poltorak M, Kulaga H, Adams AJ, Freed WJ (2993) Certain host-donor rat strain combinations do not reject brain allografts after systemic sensitization. Exp Neurol 122:48–56Google Scholar
  15. 15.
    Jiang LQ, Hamasaki D (1994) Corneal electroretinographic function rescued by normal retinal pigment epithelial grafts in retinal degenerative Royal College of Surgeons rats. Invest Ophthalmol Vis Sci 35:4300–4309Google Scholar
  16. 16.
    Jiang LQ, Jorquera M, Streilein JW (1993) Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci 34:3347–3354Google Scholar
  17. 17.
    Kaplan HJ, Stevens TR (1978) A reconsideration of immunologic privilege within the anterior chamber of the eye. Transplantation 19: 302–309Google Scholar
  18. 18.
    LaVail MM, Li L, Turner JE, Yasumura D (1992) Retinal pigment epithelial cell transplantation in RCS rats: normal metabolism in rescued photoreceptors. Exp Eye Res 55: 555–562Google Scholar
  19. 19.
    Lewis GP, Guerin CJ, Anderson DH, Matsumoto B, Fisher SK (1994) Rapid changes in the expression of glial cell proteins caused by experimental retinal detachment. Am J Ophthalmol 118: 368–376Google Scholar
  20. 20.
    Machemer R (1987) Experimental retinal detachment in the owl monkey. II. Histology of the retina and pigment epithelium. Am J Ophthalmol 66:396–402Google Scholar
  21. 21.
    Medawar PB (1948) Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to anterior chamber of the eye. Br J Exp Pathol 29: 58–69Google Scholar
  22. 22.
    Niederkorn JY (1990) Immune privilege and immune regulation in the eye. Adv Immunol 48:19–226Google Scholar
  23. 23.
    Paul LC, Zaltzman JS (1996) Clinical diagnosis of chronic rejection. In: Solez K, Racusen LC, Billingham ME (eds) Solid organ transplant rejection. Dekker, New York, pp 1–57Google Scholar
  24. 24.
    Poltorok M, Freed WJ (1991) Bn rats do not reject F344 brain allografts even after systemic sensitization. Ann Neurol 29:378–388Google Scholar
  25. 25.
    Rao O, Lund RD, Kunz HW, Gill TJ III (1988) Immunological implications of xenogeneic and allogeneic transplantation to neonatal rats. Prog Brain Res 78:281–286Google Scholar
  26. 26.
    Raju S, Grogan JB (1977) Immunologic study of the brain as a privileged site. Transplant Proc 9: 1187–1191Google Scholar
  27. 27.
    Sefton AJ, Lund RD (1988) Cotransplantation of embryonic mouse retina, with tectum, diencephalon, or cortex to neonatal rat cortex. J Comp Neurol 269:548–564Google Scholar
  28. 28.
    Sheng Y, Gouras P, Cao H (1995) Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. Invest Ophthalmol Vis Sci 36:381–390Google Scholar
  29. 29.
    Sheng Y, Li W, Cao H, Lin P-K, Lavid J, Saeki M, Gouras P (1995) Intravitreal cyclosporine prevents RPE xenograft rejection in rabbit retina. Invest Ophthalmol Vis Sci 36[Suppl]:S250Google Scholar
  30. 30.
    Streilein JW, Wilbanks GA, Cousins SW (1992) Immunoregulatory mechanisms of the eye. J Neuroimmunol 39:185–200Google Scholar
  31. 31.
    Tompsett E, Abi-Hanna D, Wakefield D (1990) Immunological privilege in the eye: a review. Curr Eye Res 9:1141–1145Google Scholar
  32. 32.
    Yamamoto S, Du J, Gouras P, Kjeldbye H (1993) Retinal pigment epithelial transplants and retinal function in RCS rats. Invest Ophthalmol Vis Sci 34:3068–3075Google Scholar
  33. 33.
    Yang P, deVos AF, Kijstra A (1996) Macrophages in the retina of normal Lewis rats and their dynamics after injection of lipopolysaccharide. Invest Ophthalmol Vis Sci 37:77–85Google Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Lennart Berglin
    • 1
  • Peter Gouras
    • 2
  • Yoahua Sheng
    • 2
  • Javier Lavid
    • 2
  • Po-Kang Lin
    • 2
  • Huiyun Cao
    • 2
  • Hild Kjeldbye
    • 2
  1. 1.St. Eriks Hospital, The Karolinska InstituteStockholmSweden
  2. 2.Department of OphthalmologyNew YorkUSA

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