Stem cell based therapies for age-related macular degeneration: The promises and the challenges |
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| Affiliation: | 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;1. Jules Stein Eye Institute Retina Division, and David Geffen School of Medicine, University of California, Los Angeles, CA, USA;2. Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA;3. Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA;4. Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, MA, USA;5. Advanced Cell Technology, Marlborough, MA, USA;6. Storm Eye Institute, Medical University of South Carolina, Charleston, SC, USA;1. Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford and Oxford University Eye Hospital, NHS Foundation Trust, NIHR Biomedical Research Centre, Oxford, United Kingdom;2. Moorfields Eye Hospital, NHS Foundation Trust, NIHR Biomedical Research Centre, London, United Kingdom;3. Center for Advanced Retinal and Ocular Therapeutics, Department of Ophthalmology, The Children''s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;4. Retina Division, Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California;3. Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106;4. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106;6. Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106, Japan;5. Polgenix, Inc., Cleveland, Ohio 44106, Japan;1. Richard E Hoover Low Vision Rehabilitation Services, Greater Baltimore Medical Center, Baltimore, MD 21204, USA;2. Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, MD 21204, USA;1. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA;2. Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA;3. David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095, USA |
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| Abstract: | ![]()
Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed. |
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| Keywords: | Age-related macular degeneration Human embryonic stem cell-derived retinal pigment epithelium Induced pluripotent stem cell-derived retinal pigment epithelium Stem cell-derived retinal progenitor cell ACT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0035" }," $$" :[{" #name" :" text" ," _" :" Advanced Cell Technology AMD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" age-related macular degeneration APC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" antigen processing cell ARMS2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" age-related macular degeneration susceptibility gene 2 ATP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" adenosine triphosphate AR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" acute rejection BCVA" },{" #name" :" keyword" ," $" :{" id" 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