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Perspektive: Tissue engineering bei RPE-Transplantation in AMD

Perspective: Tissue engineering for RPE transplantation in AMD

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Summary

The Retinal pigment epithelium (RPE) incurs a lifelong damage, which is one mechanism leading to age-related macular degeneration (AMD), the most common cause of blindness over 55. Despite intense research, to date the majority of those affected have no effective therapy available. Cell based replacement strategies of the RPE represent, in contrast to current pharmacologic interventions, a curative treatment. This article describes potential future perspectives of current autologous clinical RPE transplantation protocols. Intermittent culturing could potentially rejuvenate aged RPE. Age related changes of the RPE are reflected in culture, yet our findings suggest that they can be overcome with modern artificial substrates and defined culture media. Degenerations and surgical damage in Bruch's membrane may potentially compromise survival or function of transplanted RPE. Hence, an important adjunct to RPE replacement is Bruch's membrane prosthesis, for which we dedicated a significant proportion of this manuscript. Results of our in vitro and in vivo studies with amniotic membrane, porous polyester membranes and electrospun nanofibers are briefly summarized. We conclude with an outlook on future research on the use of tissue engineering for replacement of the entire RPE/Choriocapillaris Complex, and on promising results from stem cell derived RPE-like cells.

Zusammenfassung

Ein lebenslang kumulierender Schaden am Retinalen Pigment Epithel (RPE) bedingt unter anderem die altersbedingte Makula Degeneration, die häufigste Erblindungsursache ab 55. Trotz intensiver Forschung, gibt es bis heute für den Großteil der Betroffenen keine effektive Therapie. Zell basierte Ersatz Strategien des RPE stellen, im Gegensatz zu derzeitigen pharmakologischen Interventionen, eine kurative Therapieoption dar. Dieser Artikel behandelt mögliche Zukunfts-Perspektiven von mittlerweile klinisch praktizierten autologen RPE Transplantations-Protokollen. Durch zwischenzeitliche Zell Kultur könnte man eine Verjüngung der Zellen erreichen. Obwohl altersbedingte Veränderungen der RPE Zelle auch für die Kultur ein Hindernis sind, fanden wir dass dies mit modernen Zellkultur Substraten und definierten Kulturmedien möglicherweise überwindbar ist. Degenerationen und chirurgisches Trauma der Bruch'schen Membran verhindern möglicherweise überleben und/oder Transplantat Funktion. Ein wesentlicher Aspekt des RPE Ersatz ist somit auch ein prothetischer Ersatz der Bruch'schen Membran, wofür ein wesentlicher Teil dieses Artikels gewidmet wurde. Wir stellen zusammenfassend Erkenntnisse aus Untersuchungen mit Amnion Membran, porösen synthetischen Polyestern, sowie elektrogesponnenen Nanofasern vor. Abschließend wird die Bedeutung dieser Ergebnisse für zukünftige Forschungsziele, wie der Einsatz von Tissue engineering für Rekonstruktion des gesamten RPE/Choriocapillaris Komplex sowie hoffnungsreiche Daten über aus Stammzellen in vitro differenzierte RPE ähnliche Zellen diskutiert.

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Literatur

  • Steinberg RH, Wood I (1979) The relationship of the retinal pigment epithelium to photoreceptor outer segments in human retina. In: KM Zinn, MF Marmor, (eds) The retinal pigment epithelium. Harvard University Press, Cambridge/MA: pp 32–44

    Google Scholar 

  • Strauss O (2005) The retinal pigment epithelium in visual function. Physiol Rev 85(3): 845–881

    Article  PubMed  CAS  Google Scholar 

  • Young RW (1987) Pathophysiology of age-related macular degeneration. Surv Ophthalmol 31(5): 291–306

    Article  PubMed  CAS  Google Scholar 

  • Klein R, Klein BE, Linton KL (1992) Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 99(6): 933–943

    PubMed  CAS  Google Scholar 

  • Zarbin MA (2004) Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 122(4): 598–614

    Article  PubMed  Google Scholar 

  • Scholl HP, Fleckenstein M, Charbel Issa P, et al (2007) An update on the genetics of age-related macular degeneration. Mol Vis 13: 196–205

    PubMed  CAS  Google Scholar 

  • Patel N, Adewoyin T, Chong NV (2007) Age-related macular degeneration: a perspective on genetic studies. Eye May 11; [Epub ahead of print]

  • Martidis A, Tennant MTS (2004) Age-related macular degeneration. In: M Yanoff, JS Duker (eds) Ophthalmology, 2nd edn. Mosby, St.Louis, pp 925–933

    Google Scholar 

  • Schmidt-Erfurth UM, Pruente C (2007) Management of neovascular age-related macular degeneration. Prog Retin Eye Res 26(4): 437–451

    Article  PubMed  CAS  Google Scholar 

  • Binder S, Stanzel BV, Krebs I, Glittenberg C (2007) Transplantation of the RPE in AMD. Prog Retin Eye Res 26(5): 516–554

    Article  PubMed  Google Scholar 

  • Del Priore LV, Tezel TH, Kaplan HJ (2006) Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula. Prog Retin Eye Res 25(6): 539–562

    Article  PubMed  Google Scholar 

  • Abe T, Yoshida M, Yoshioka Y, et al (2007) Iris pigment epithelial cell transplantation for degenerative retinal diseases. Prog Retin Eye Res 26(3): 302–321

    Article  PubMed  CAS  Google Scholar 

  • Lund RD, Kwan AS, Keegan DJ, et al (2001) Cell transplantation as a treatment for retinal disease. Prog Retin Eye Res 20(4): 415–449

    Article  PubMed  CAS  Google Scholar 

  • Binder S, Krebs I, Hilgers RD, et al (2004) Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 45(11): 4151–4160

    Article  PubMed  Google Scholar 

  • Van Meurs JC, Vijfvinkel G, Misotten T, et al (2006) The translocation of an autologous retinal pigment epithelium and choroid graft in patients with exudative macular degeneration: visual results. Invest Ophthalmol Vis Sci 47(5): 2692

    Google Scholar 

  • Boulton M, Roanowska M, Wess T (2004) Ageing of the retinal pigment epithelium: implications for transplantation. Graefes Arch Clin Exp Ophthalmol 242(1): 76–84

    Article  PubMed  Google Scholar 

  • Hu J, Bok D (2001) A cell culture medium that supports the differentiation of human retinal pigment epithelium into functionally polarized monolayers. Molecular Vision 7: 14–19

    PubMed  CAS  Google Scholar 

  • MacLaren RE, Uppal GS, Balaggan KS, et al (2007) Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration. Ophthalmology 114(3): 561–570

    Article  PubMed  Google Scholar 

  • Stanzel BV, Binder S, Blumenkranz MS, Marmor MF (2006) Culture of Human RPE From Aged Donors on a Potential Bruch's Membrane Prosthesis. Invest Ophthalmol Vis Sci 47(5): 1407

    Google Scholar 

  • Bandyopadhyay D, Medrano EE (2003) The emerging role of epigenetics in cellular and organismal aging. Exp Gerontol 38(11–12): 1299–1307

    Article  PubMed  CAS  Google Scholar 

  • Burke JM, Hjelmeland LM (2005) Mosaicism of the retinal pigment epithelium: seeing the small picture. Mol Interv 5(4): 241–249

    Article  PubMed  Google Scholar 

  • Ohno-Matsui K, Ichinose S, Nakahama K, et al (2005) The effects of amniotic membrane on retinal pigment epithelial cell differentiation. Mol Vis 11: 1–10

    PubMed  CAS  Google Scholar 

  • Rak DJ, Hardy KM, Jaffe GJ, McKay BS (2006) Ca(++)-switch induction of RPE differentiation. Exp Eye Res 82(4): 648–656

    Article  PubMed  CAS  Google Scholar 

  • Tezel TH, Del Priore LV, Kaplan HJ (2004) Reengineering of aged Bruch's membrane to enhance retinal pigment epithelium repopulation. Invest Ophthalmol Vis Sci 45(9): 3337–3348

    Article  PubMed  Google Scholar 

  • Gullapalli VK, Sugino IK, Van Patten Y, et al (2005) Impaired RPE survival on aged submacular human Bruch's membrane. Exp Eye Res 80(2): 235–248

    Article  PubMed  CAS  Google Scholar 

  • Stanzel BV, Espana EM, Grueterich M, et al (2005) Amniotic membrane maintains the phenotype of rabbit retinal pigment epithelial cells in culture. Exp Eye Res 80(1): 103–112

    Article  PubMed  CAS  Google Scholar 

  • Sippel KC, Ma JJ, Foster CS (2001) Amniotic membrane surgery. Curr Opin Ophthalmol 12(4): 269–281

    Article  PubMed  CAS  Google Scholar 

  • Tseng SC, Tsubota K (2001) Amniotic membrane transplantation for ocular surface reconstruction. In: EJ Holland, MJ Mannis (eds) Ocular surface diseases: medical and surgical management. Springer, pp 226–231

  • Abri A, Binder S, Assadoullina A, et al (2005) Transplantation of human amniotic membrane and ex vivo expanded homologous retinal pigment epithelial cells on human amniotic membrane into subretinal space of New Zealand White Rabbits. Invest Ophthalmol Vis Sci 46(5): 4146

    Google Scholar 

  • Maminishkis A, Chen S, Jalickee S, et al (2006) Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue. Invest Ophthalmol Vis Sci 47(8): 3612–3624

    Article  PubMed  Google Scholar 

  • Ma Z, Kotaki M, Inai R, Ramakrishna S (2005) Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng 11(1–2): 101–109

    Article  PubMed  Google Scholar 

  • Venugopal J, Ramakrishna S (2005) Applications of polymer nanofibers in biomedicine and biotechnology. Appl Biochem Biotechnol 125(3): 147–158

    Article  PubMed  CAS  Google Scholar 

  • He W, Yong T, Teo WE, et al (2005) Fabrication and endothelialization of collagen-blended biodegradable polymer nanofibers: potential vascular graft for blood vessel tissue engineering. Tissue Eng 11(9–10): 1574–1588

    Article  PubMed  CAS  Google Scholar 

  • Schindler M, Ahmed I, Kamal J, et al (2005) A synthetic nanofibrillar matrix promotes in vivo-like organization and morphogenesis for cells in culture. Biomaterials 26(28): 5624–5631

    Article  PubMed  CAS  Google Scholar 

  • Venugopal J, Low S, Choon AT, Ramakrishna S (2007) Interaction of cells and nanofiber scaffolds in tissue engineering. J Biomed Mater Res B Appl Biomater May 3; [Epub ahead of print]

  • Stanzel BV, Huie P, Blumenkranz MS, et al (2007) Towards prosthetic replacement of Bruch's membrane: comparison of polyester and electrospun nanofiber membranes. Invest Ophthalmol Vis Sci 48(5): 5085

    Google Scholar 

  • Molnar FE, Lombardi L, Berker N, et al (2005) Synthetic Bruch's membrane substitutes: comparisons after subretinal transplantation with cultured iris pigment epithelium. Invest Ophthalmol Vis Sci 46(5): 4154

    Google Scholar 

  • Yellachich D, Leng T, Huie P, et al (2004) Autologous iris pigment epithelium cultured on cellulose acetate membrane transplanted into the subretinal space of rabbits. ARVO Meeting Abstracts 45(5): 5168

    Google Scholar 

  • Kent D, Sheridan C (2003) Choroidal neovascularization: a wound healing perspective. Mol Vis 9: 747–755

    PubMed  CAS  Google Scholar 

  • Bhatt NS, Newsome DA, Fenech T, et al (1994) Experimental transplantation of human retinal pigment epithelial cells on collagen substrates. Am J Ophthalmol 117(2): 214–221

    PubMed  CAS  Google Scholar 

  • Thumann G, Hueber A, Dinslage S, et al (2006) Characteristics of iris and retinal pigment epithelial cells cultured on collagen type I membranes. Curr Eye Res 31(3): 241–249

    Article  PubMed  CAS  Google Scholar 

  • Thumann G, Aisenbrey S, Schaefer F, Bartz-Schmidt KU (2006) Instrumentation and technique for delivery of tissue explants to the subretinal space. Ophthalmologica 220(3): 170–173

    Article  PubMed  Google Scholar 

  • Fisher RF (1987) The influence of age on some ocular basement membranes. Eye 1 (Pt 2): 184–189

    PubMed  Google Scholar 

  • Marshall J, Hussain A, Starita C, et al (1998) Aging and Bruch's membrane. In: Marmor MF, Wolfensberger TJ (eds) The retinal pigment epithelium: function and disease. Oxford University Press, New York, Oxford, pp 669–692

    Google Scholar 

  • van Meurs JC, Van Den Biesen PR (2003) Autologous retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: short-term follow-up. Am J Ophthalmol 136(4): 688–695

    Article  PubMed  Google Scholar 

  • Joussen AM, Heussen FM, Joeres S, et al (2006) Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration. Am J Ophthalmol 142(1): 17–30

    Article  PubMed  Google Scholar 

  • Treumer F, Bunse A, Klatt C, Roider J (2007) Autologous retinal pigment epithelium-choroid sheet transplantation in age related macular degeneration: morphological and functional results. Br J Ophthalmol 91(3): 349–353

    Article  PubMed  Google Scholar 

  • Maaijwee KJM, van Meurs JC, Kirchhof B, et al (2006) Histological evidence for revascularization of an autologous RPE-choroid graft in the pig. Br J Ophthalmol:bjo.2006.103259

  • Sakamoto T, Sakamoto H, Murphy TL, et al (1995) Vessel formation by choroidal endothelial cells in vitro is modulated by retinal pigment epithelial cells. Arch Ophthalmol 113(4): 512–520

    PubMed  CAS  Google Scholar 

  • Fan W, Zheng JJ, McLaughlin BJ (2002) An in vitro model of the back of the eye for studying retinal pigment epithelial-choroidal endothelial interactions. In Vitro Cell Dev Biol Anim 38(4): 228–234

    Article  PubMed  CAS  Google Scholar 

  • Haruta M, Sasai Y, Kawasaki H, et al (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 

  • Enzmann V, Howard RM, Yamauchi Y, et al (2003) Enhanced induction of RPE lineage markers in pluripotent neural stem cells engrafted into the adult rat subretinal space. Invest Ophthalmol Vis Sci 44(12): 5417–5422

    Article  PubMed  Google Scholar 

  • Atmaca-Sonmez P, Li Y, Yamauchi Y, et al (2006) Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage. Exp Eye Res 83(5): 1295–1302

    Article  PubMed  CAS  Google Scholar 

  • Harris JR, Brown GA, Jorgensen M, et al (2006) Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury. Invest Ophthalmol Vis Sci 47(5): 2108–2113

    Article  PubMed  Google Scholar 

  • Klimanskaya I, Hipp J, Rezai KA, et al (2004) Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells 6(3): 217–245

    PubMed  CAS  Google Scholar 

  • Lund RD, Wang S, Klimanskaya I, et al (2006) Human Embryonic Stem Cell-Derived Cells Rescue Visual Function in Dystrophic RCS Rats. Cloning Stem Cells 8(3): 189–199

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Stanford University, Stanford, CA, USA

    B. V. Stanzel, M. Englander, S. S. Sanislo, P. Huie, M. S. Blumenkranz & M. F. Marmor

  2. L. Boltzmann Institute für Retinologie and biomikroskopische Laserchirurgie, Wien, Austria

    B. V. Stanzel & S. Binder

  3. Department of Genetics, Stanford University, Stanford, CA, USA

    D. J. Strick

Authors
  1. B. V. Stanzel
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  2. M. Englander
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  3. D. J. Strick
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  4. S. S. Sanislo
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  5. P. Huie
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  6. M. S. Blumenkranz
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  7. S. Binder
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  8. M. F. Marmor
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Correspondence to B. V. Stanzel.

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Stanzel, B., Englander, M., Strick, D. et al. Perspektive: Tissue engineering bei RPE-Transplantation in AMD. Spektrum Augenheilkd. 21, 212–217 (2007). https://doi.org/10.1007/s00717-007-0213-1

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  • DOI: https://doi.org/10.1007/s00717-007-0213-1

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