Skip to main content

Advertisement

Springer Nature Link
Log in

Transplantation of RPE in age-related macular degeneration: Observations in disciform lesions and dry RPE atrophy

  • Clinical Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

• A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). • Methods: Patches of human fetal RPE (13–20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8–20 months. • Results: In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1–6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. • Conclusion: Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of time

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Google Scholar 

  2. Algvere PV, Berglin L, Gouras P, Sheng Y (1995) Transplantation of human RPE in age-related macular degeneration with subfoveal neovascularization. Invest Ophthalmol Vis Sci 36:S211

    Google Scholar 

  3. Anderson DH, Guerin CJ, Erickson PA, Stern WH, Fisher SK (1986) Morphological recovery in the reattached retina. Invest Ophthalmol Vis Sci 27:168–183

    PubMed  Google Scholar 

  4. Bynoe LA, Chang TS, Funata M, Del Priore LV, Kaplan HJ, Green WR (1994) Histopathologic examination of vascular patterns in subfoveal neovascular membranes. Ophthalmology 101:1112–1117

    PubMed  Google Scholar 

  5. Campochiaro PA, Hacket SF, Conway BP (1991) Retinoic acid promotes density-dependent growth arrest in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 32:65–72

    PubMed  Google Scholar 

  6. Das SR, Bhardwaj N, Gouras P (1990) Synthesis of retinoids by human retinal epithelium and transfer to rod outer segments. Biochem J 268:201–206

    PubMed  Google Scholar 

  7. Del Priore LV, Hornbeck R, Kaplan HJ, Jones Z, Silverman MS, Mosinger-Ogilvie J, Swinn M (1995) Debridement of the pig retinal pigment epithelium in vivo. Arch Ophthalmol 113:939–944

    PubMed  Google Scholar 

  8. Della NG, Campochiaro PA, Zack DJ (1996) Localization of TIMP-3 mRNA expression to the retinal pigment epithelium. Invest Ophthalmol Vis Sci 37:S1143

    Google Scholar 

  9. Dorey CK, Wu G, Ebenstein D, Garsd A, Weiter JJ (1989) Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Invest Ophthalmol Vis Sci 30:1691–1699

    PubMed  Google Scholar 

  10. 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 230:292–300

    Google Scholar 

  11. Garner A, Sarks S, Sarks JP (1994) Degenerative and related disorders of the retina and choroid. In: Garner E, Klintworth GK (eds) Pathobiology of ocular disease, 2nd edn. Dekker, New York, pp 631–674

    Google Scholar 

  12. Glaser BM, Lemor M (1994) Pathobiology of proliferative vitreoretinopathy. In: Ryan SJ, Glaser BM (eds) Retina, 2nd edn. Mosby — Year Book, St. Louis, vol 3, pp 2254–2257

    Google Scholar 

  13. Gouras P, Berglin L, Sheng Y, Cao H, Lavid J, Lin P-K, Bergman L, Kjeldbye H (1995) Long term human RPE transplants in monkey retina. Invest Ophthalmol Vis Sci 36:S211

    Google Scholar 

  14. Green WR, Enger C (1993) Age-related macular degeneration histopathology studies. The 1992 Lorenz E Zimmerman Lecture. Ophthalmology 100:1519–1535

    PubMed  Google Scholar 

  15. Grierson I, Hiscott P, Hogg P, Robey H, Mazure A, Larkin G (1994) Development, repair and regeneration of the retinal pigment epithelium. Eye 8:255–262

    PubMed  Google Scholar 

  16. Guerin C, Lewis P, Fisher SK, Anderson DH (1993) Recovery of pbotoreceptor outer segment length and analysis of membrane assembly rates in regenerating primate photoreceptor outer segments. Invest Ophthalmol Vis Sci 34:175–183

    PubMed  Google Scholar 

  17. Hasson T, Heintzelman MB, Santos-Sacchi J, Corey DP, Mooseker MS (1995) Expression in cochlea and retina of myosin VII, the gene product defective in Usher syndrome type 1B. Proc Natl Acad Sci USA 92:9815–9819

    PubMed  Google Scholar 

  18. 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 35:4300–4309

    PubMed  Google Scholar 

  19. Jiang LQ, Jorquera M, Streilein JW (1993) Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. Invest Ophthalmol Vis Sci 34:3347–3354

    PubMed  Google Scholar 

  20. Jiang LQ, Jorquera M, Streilein JW (1994) Immunologic consequences of intraocular implantation of retinal pigment epithelial allografts. Exp Eye Res 58:719–728

    PubMed  Google Scholar 

  21. 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 55:555–562

    PubMed  Google Scholar 

  22. 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

    PubMed  Google Scholar 

  23. Little CW, Castillo BV, DiLoreto DA, Cox C, Wyatt J, del Cerro C, del Cerro M (1996) Transplantation of human fetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina. Invest Ophthalmol Vis Sci 37:204–211

    PubMed  Google Scholar 

  24. Lopez PF, Grossniklaus HE, Lambert M, Aaberg TM, Capone A Jr, Sternberg P Jr, L'Hernault N (1991) Pathological features of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 112:647–656

    PubMed  Google Scholar 

  25. Lopez R, Gouras P, Kjeldbye H et al. (1989) Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Invest Ophthalmol Vis Sci 30:586–588

    PubMed  Google Scholar 

  26. Mazure A, Grierson I (1992) In vitro studies of the contractility of cell types involved in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci 33:3407–3416

    PubMed  Google Scholar 

  27. Seregard S, Algvere PV, Berglin L (1994) Immunohistochemical characterization of surgically removed subfoveal fibrovascular membranes. Graefe's Arch Clin Exp Ophthalmol 232:325–329

    Google Scholar 

  28. Sheng Y, Gouras P, Cao H, Berglin L, Kjeldbye H, Lopez R, Rosskothen H (1995) Patch transplants of human fetal retinal pigment epithelium in rabbit and monkey retina. Invest Ophthalmol Vis Sci 36:381–390

    PubMed  Google Scholar 

  29. Sheraidah G, Steinmetz R, Maguire J, Pauleikhoff D, Marshall J, Bird AC (1993) Correlation between lipids extracted from Bruch's membrane and age. Ophthalmology 100:47–51

    PubMed  Google Scholar 

  30. Valentino A, Kaplan HJ, Del Priore LV, Fang J, Berger A, Silverman MS (1995) Retinal pigment epithelium repopulation and photoreceptor repair after submacular surgery. Arch Ophthalmol 113:932–938

    PubMed  Google Scholar 

  31. Weber BH, Vogt G, Pruett RC, Stohr H, Felbor U (1994) Mutations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) in patients with Sorsby's fundus dystrophy. Nature Genet 8:352–356

    PubMed  Google Scholar 

  32. Weil D, Blanchard S, Kaplan J, Guilford P, Walsh J et al. (1995) Defective myosin VIIa gene responsible for Usher's syndrome Type 1B. Nature (Lond) 374:60–61

    Google Scholar 

  33. Yamamoto S, Du J, Gouras P, Kjeldbye H (1993) Retinal pigment epithelial transplants and retinal function in RCS rats. Invest Ophthalmol Vis Sci 34:3068–3075

    PubMed  Google Scholar 

  34. Young RW (1987) Pathophysiology of age-related macular degeneration. Surv Ophthalmol 31:291–306

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Karolinska Institute, St. Erik's Eye Hospital, Fleminggatan 22, S-11282, Stockholm, Sweden

    Peep V. Algvere, Lennart Berglin & Eva Dafgård Kopp

  2. Department of Ophthalmology, Columbia University, New York, N.Y., USA

    Peter Gouras & Yaohua Sheng

Authors
  1. Peep V. Algvere
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lennart Berglin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Gouras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yaohua Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eva Dafgård Kopp
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by grants from the Swedish Medical Research Council (B96-12X-11561-01A) and the Crown Princess Margareta Foundation, Stockholm, Sweden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Algvere, P.V., Berglin, L., Gouras, P. et al. Transplantation of RPE in age-related macular degeneration: Observations in disciform lesions and dry RPE atrophy. Graefe's Arch Clin Exp Ophthalmol 235, 149–158 (1997). https://doi.org/10.1007/BF00941722

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00941722

Keywords

Search

Navigation