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Stem cell based therapies for age-related macular degeneration: The promises and the challenges.
Prog Retin Eye Res. 2015 Sep; 48:1-39.PR

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.

Authors+Show Affiliations

USC Eye Institute, University of Southern California, 1450 Biggy Street, NRT7510, Los Angeles, CA 90033, USA. Electronic address: h.nazari.k@gmail.com.USC Eye Institute, University of Southern California, MMR123, Los Angeles, CA 90033, USA. Electronic address: drzhangli@hotmail.com.USC Eye Institute, University of Southern California, 1450 Biggy Street, NRT7510, Los Angeles, CA 90033, USA. Electronic address: dzhu@med.usc.edu.USC Eye Institute, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA. Electronic address: gchader02040@gmail.com.USC Eye Institute, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA. Electronic address: paulofalabella@hotmail.com.USC Eye Institute, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA. Electronic address: frstefanini@gmail.com.Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver Anschutz Medical Campus, 12700 East 19th Avenue, F442, Aurora, CO 80045-2507, USA. Electronic address: teisha.rowland@ucdenver.edu.Center for Stem Cell Biology and Engineering, Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA. Electronic address: clegg@lifesci.ucsb.edu.USC Eye Institute, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA. Electronic address: ahkashan@med.usc.edu.USC Eye Institute, University of Southern California, 1450 Biggy Street, NRT7503, Los Angeles, CA 90033, USA. Electronic address: dhinton@med.usc.edu.USC Eye Institute, Institute for Biomedical Therapeutics, University of Southern California, 1441 Eastlake Avenue, NTT 4463, Los Angeles, CA 90033, USA. Electronic address: Humayun@med.usc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26113213

Citation

Nazari, Hossein, et al. "Stem Cell Based Therapies for Age-related Macular Degeneration: the Promises and the Challenges." Progress in Retinal and Eye Research, vol. 48, 2015, pp. 1-39.
Nazari H, Zhang L, Zhu D, et al. Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Prog Retin Eye Res. 2015;48:1-39.
Nazari, H., Zhang, L., Zhu, D., Chader, G. J., Falabella, P., Stefanini, F., Rowland, T., Clegg, D. O., Kashani, A. H., Hinton, D. R., & Humayun, M. S. (2015). Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Progress in Retinal and Eye Research, 48, 1-39. https://doi.org/10.1016/j.preteyeres.2015.06.004
Nazari H, et al. Stem Cell Based Therapies for Age-related Macular Degeneration: the Promises and the Challenges. Prog Retin Eye Res. 2015;48:1-39. PubMed PMID: 26113213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stem cell based therapies for age-related macular degeneration: The promises and the challenges. AU - Nazari,Hossein, AU - Zhang,Li, AU - Zhu,Danhong, AU - Chader,Gerald J, AU - Falabella,Paulo, AU - Stefanini,Francisco, AU - Rowland,Teisha, AU - Clegg,Dennis O, AU - Kashani,Amir H, AU - Hinton,David R, AU - Humayun,Mark S, Y1 - 2015/06/23/ PY - 2015/03/25/received PY - 2015/06/05/revised PY - 2015/06/11/accepted PY - 2015/6/27/entrez PY - 2015/6/27/pubmed PY - 2016/4/20/medline KW - Age-related macular degeneration KW - Human embryonic stem cell-derived retinal pigment epithelium KW - Induced pluripotent stem cell-derived retinal pigment epithelium KW - Stem cell-derived retinal progenitor cell SP - 1 EP - 39 JF - Progress in retinal and eye research JO - Prog Retin Eye Res VL - 48 N2 - 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. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/26113213/Stem_cell_based_therapies_for_age_related_macular_degeneration:_The_promises_and_the_challenges_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(15)00046-4 DB - PRIME DP - Unbound Medicine ER -