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Transplantation of cultured human retinal pigment epithelium into rabbit subretina

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Abstract

Transplantation of normal retinal pigment epithelium (RPE) into a diseased eye holds promise for treatment of several blinding disorders. Previuos studies have involved immunosuppression and implantation of freshly isolated cells. We report here the successful transplantation of cultured human RPE cells into rabbits that were not immunosuppressed. A modified pars plana transvitreal technique was used for RPE transplantation. The cultured RPE cells, loaded with carbon as a marker, were transplanted into the denuded Bruch's membrane of albino rabbits. The animals were followed for from 1 week to 3 months. On histologic examination at 2 months, no infiltrating lymphocytes were found in the vitreous cavity or choroid, even though Bruch's membrane was damaged. At about 3 months there were some macrophages in the subretina of transplanted eyes, indicating that an immunoreaction does occur eventually. Electron microscopy of the transplanted RPE showed apical-basal polarity and gap junctions. Restored function was attested to by the presence of phagosomes and phagocytosed outer segments in the transplanted cells. Our findings suggest that there is a weak, delayed immunoreaction to human RPE cells transplanted beneath the retina of the rabbit; however, functional recovery of the transplanted cells occurs before this immune response develops.

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References

  1. Aramant R, Seiler M, Ehinger B, Bergström A, Gustavii B, Brundin P, Adolph A (1990) Xenografting human fetal retina to adult rat retina. Invest Ophthalmol Vis Sci [Suppl] 31:594

    Google Scholar 

  2. Bok D, Hall MO (1971) The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat. J Cell Biol 49:664–682

    Google Scholar 

  3. Brittis M, Gouras P, Lopez R, Sullivan B, Kjeldbye H (1988) Retinal epithelial allografts of longer duration facilitated by cyclosporine. Invest Ophthalmol Vis Sci [Suppl] 29:241

    Google Scholar 

  4. Caspi RR, Roberge FG, Nussenblatt RB (1987) Organ-resident, nonlymphoid cells suppress proliferation of autoimmune T-helper lymphocytes. Science 237:1029–1032

    Google Scholar 

  5. Chu HH, Berman DH, Khan YS, Garrett CW, Zhang BX, Garcia CA (1990) Relative immune privilege of rat-rabbit RPE xenograft in the subretinal space. Invest Ophthalmol Vis Sci [Suppl] 31:596

    Google Scholar 

  6. Cousins SW, McCabe MM, Danielpour D, Streilein JW (1991) Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 32:2201–2211

    Google Scholar 

  7. Danaief J, Kwun R, Bhardwaj N, Lopez K, Coff S, Gouras P (1991) Genetically labelled RPE transplanted to RCS rat retina: a paradigm for gene transfer into the retina. Invest Ophthalmol Vis Sci [Suppl] 32:982

    Google Scholar 

  8. Del Cerro M, Lazar E, Grover DA, Gallagher MJ, Sladek CD, Chu J, del Cerro C (1990) Intraocular transplantation and culture of human embryonic retinal cells. Invest Ophthalmol Vis Sci [Suppl] 31:593

    Google Scholar 

  9. El Dirini AA, Wang H, Ogden TE, Ryan SJ (1991) Retinal pigment epithelium (RPE) implantation in the rabbit: technique and morphology. Invest Ophthalmol Vis Sci [Suppl] 32:668

    Google Scholar 

  10. Gartner S, Henkind P (1982) Pathology of retinitis pigmentosa. Ophthalmology 89:1425–1432

    Google Scholar 

  11. Gaur V, Agarwal N, Turner JE (1990) Maintenance of visual gene expression following RPE transplantation in RCS rat retina. Invest Ophthalmol Vis Sci [Suppl] 31:596

    Google Scholar 

  12. Glaser BM, Campochiaro PA, Davis JL, Sato M (1985) Retinal pigment epithelial cells release an inhibitor of neovascularization. Arch Ophthalmol 103:1870–1875

    Google Scholar 

  13. Gouras P, Lopez R (1989) Transplantation of retinal epithelial cells. Invest Ophthalmol Vis Sci 30:1681–1683

    Google Scholar 

  14. Gouras P, Flood MT, Eggers HM, Kjeldbye HM (1983) Transplantation of human retinal epithelium to Bruch's membrane of monkey eye. Invest Ophthalmol Vis Sci [Suppl] 24:142

    Google Scholar 

  15. Gouras P, Flood MT, Kjeldbye H, Bilek MK, Eggers HM (1985) Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye. Curr Eye Res 4:253–265

    Google Scholar 

  16. Hollyfield JG, Witkovsky P (1974) Pigmented retinal epithelium involvement in photoreceptor development and function. J Exp Zool 189:357–378

    Google Scholar 

  17. Kirchhof B, Kirchhof E, Ryan SJ, Dixon JFP, Barton BE, Sorgente N (1989) Macrophage modulation of retinal pigment epithelial cell migration and proliferation. Graefes Arch Clin Exp Ophthalmol 227:60–66

    Google Scholar 

  18. Lane C, Boulton M, Bridgman A, Marshall J (1988) Transplantation of retinal pigment epithelium in the miniature pig. Invest Ophthalmol Vis Sci [Suppl] 29:405

    Google Scholar 

  19. Lane C, Boulton M, Marshall J (1989) Transplantation of retinal pigment epithelium using a pars plana approach. Eye 3:27–32

    Google Scholar 

  20. Li L, Turner JE (1988) Transplantation of retinal pigment epithelial cells to immature and adult rat hosts: short- and longterm survival characteristics. Exp Eye Res 47:771–785

    Google Scholar 

  21. Li L, Turner JE (1988) Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. Exp Eye Res 47:911–917

    Google Scholar 

  22. Li L, Turner JE (1988) Transplantation of retinal pigment epithelium to immature and adult rat hosts: short and long term survival characteristics. Invest Ophthalmol Vis Sci [Suppl] 29:241

    Google Scholar 

  23. Li L, Turner JE (1989) RPE cell transplantation in the retina of RCS dystrophic rats: EM and long-term survival characteristics of rescued photoreceptor cells. Invest Ophthalmol Vis Sci [Suppl] 30:209

    Google Scholar 

  24. Li L, Turner JE (1990) Optimum conditions for long term photoreceptor cell rescue in RCS rats: the necessity for healthy RPE transplants. Invest Ophthalmol Vis Sci [Suppl] 31:595

    Google Scholar 

  25. Lopez R, Gouras P, Brittis M, Kjeldbye H (1987) Transplantation of cultured rabbit retinal epithelium to rabbit retina using a closed-eye method. Invest Ophthalmol Vis Sci 28:1131–1137

    Google Scholar 

  26. Lopez R, Gouras P, Kjeldbye H, Sullivan B, Reppucci V, Brittis M, Wapner F, Goluboff E (1989) Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Invest Ophthalmol Vis Sci 30:586–588

    Google Scholar 

  27. Lopez R, Gouras P, Kjeldbye H, Sullivan B, Brittis M, Das SR (1990) Transplantation of human RPE cells into monkey. Invest Ophthalmol Vis Sci [Suppl] 31:594

    Google Scholar 

  28. Machemer R (1978) Pathogenesis and classification of massive periretinal proliferation. Br J Ophthalmol 62:737–747

    Google Scholar 

  29. Raymond MC, Neill JM, Thompson JT, Barnstable CJ (1991) Characterization of a transpecies monoclonal antibody to retinal pigment epithelial cell developed from human RPE. Invest Ophthalmol Vis Sci [Suppl] 32:668

    Google Scholar 

  30. Royo PE, Quay WB (1959) Retinal transplantation from fetal to maternal mammalian eye. Growth 23:313–336

    Google Scholar 

  31. Seiler M, Aramant R, Bergström A, Adolph AR (1990) Cografting retina and retinal pigment epithelium into adult rabbit retina. Invest Ophthalmol Vis Sci [Suppl] 31:596

    Google Scholar 

  32. Sheedlo HJ, Li L, Turner JE (1989) Functional and structural characteristics of photoreceptor cells rescued in RPE-cell grafted retinas of RCS dystrophic rats. Exp Eye Res 48:841–854

    Google Scholar 

  33. Streilein JW, Bradley D (1991) Analysis of immunosuppressive properties of iris and ciliary body cells and their secretory products. Invest Ophthalmol Vis Sci 32:2700–2710

    Google Scholar 

  34. Weber P, Weiter J, Dorey CK, Schepens CL (1989) Autologous transplantation of retinal pigment epithelium in the rabbit. Invest Ophthalmol Vis Sci [Suppl] 30:209

    Google Scholar 

  35. Wongpichedchai S, Weber P, Dorey CK, Weiter J (1990) Comparison of external and internal approaches for RPE transplantation. Invest Ophthalmol Vis Sci [Suppl] 31:593

    Google Scholar 

  36. Young RW, Gaur VP, Li L, Turner JE (1991) Transplantation of 5-bromodeoxyuridine (BrdU) labeled retinal pigmented epithelial (RPE) cells on Bruch's membrane in the rabbit. Invest Ophthalmol Vis Sci [Suppl] 32:982

    Google Scholar 

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Supported in part by NIH Grants EY-01545 and EY-03040, the latter a Core Grant for Vision Research

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He, S., Wang, H.M., Ogden, T.E. et al. Transplantation of cultured human retinal pigment epithelium into rabbit subretina. Graefe's Arch Clin Exp Ophthalmol 231, 737–742 (1993). https://doi.org/10.1007/BF00919290

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  • DOI: https://doi.org/10.1007/BF00919290

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