Cell replacement and visual restoration by retinal sheet transplants |
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Authors: | Magdalene J. Seiler Robert B. Aramant |
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Affiliation: | 1. Paul Flechsig Institute of Brain Research, University of Leipzig, D-04109 Leipzig, Germany;2. Institute for Pathology and Neuropathology, Department of General Pathology, University of Tübingen, Tübingen, Germany;3. Institute of Human Genetics, Department of Biology II, Ludwig-Maximilian University, Munich, Germany;4. Institute of Psychopharmacology, Central Institute for Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Germany;1. Institute of Neuroscience, National Research Council (CNR), I-56124 Pisa, Italy;2. Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, I-50135 Florence, Italy;3. Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, I-56128 Pisa, Italy;4. BIO@SNS lab, Scuola Normale Superiore di Pisa, I-56125 Pisa, Italy;1. Department of Ophthalmology, Far Eastern Memorial Hospital, Taipei, Taiwan;2. Department of Healthcare Administration and Department of Nursing, Oriental Institute of Technology, Taipei, Taiwan;3. Department of Medicine, National Yang Ming University, Taipei, Taiwan;4. Department of Medicine, National Taiwan University, Taipei, Taiwan;1. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan;2. Department of Ophthalmology, Kawasaki Medical School, Kurashiki, Okayama 701-0114, Japan;1. Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy;2. Ophthalmology, S.Bi.Bi.T. Department, University of Parma, Parma, Italy;1. USC Eye Institute, University of Southern California, 1450 Biggy Street, NRT7510, Los Angeles, CA 90033, USA;2. USC Eye Institute, University of Southern California, MMR123, Los Angeles, CA 90033, USA;3. USC Eye Institute, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA;4. Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver Anschutz Medical Campus, 12700 East 19th Avenue, F442, Aurora, CO 80045-2507, USA;5. Center for Stem Cell Biology and Engineering, Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA;6. USC Eye Institute, University of Southern California, 1450 Biggy Street, NRT7503, Los Angeles, CA 90033, USA;7. USC Eye Institute, Institute for Biomedical Therapeutics, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA |
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Abstract: | Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity.In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy. |
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