Stem cell based therapies for age-related macular degeneration: The promises and the challenges. (September 2015)

• Record Type: Journal Article
• Authors: Nazari, Hossein; Zhang, Li; Zhu, Danhong; Chader, Gerald J.; Falabella, Paulo; Stefanini, Francisco; Rowland, Teisha; Clegg, Dennis O.; Kashani, Amir H.; Hinton, David R.; Humayun, Mark S.
• Is Part Of: Progress in retinal and eye research. Volume 48(2015:Sep.)
• Page Start: 1
• Page End: 39
• Publication Date: 2015-09
• Subjects: 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 Advanced Cell Technology -- AMD age-related macular degeneration -- APC antigen processing cell -- ARMS2 age-related macular degeneration susceptibility gene 2 -- ATP adenosine triphosphate -- AR acute rejection -- BCVA best corrected visual acuity -- BM Bruch's membrane -- BMSC bone mesenchymal stem cell -- BrdU bromodeoxyuridine -- bFGF basic fibroblast growth factor -- CETP cholesterol ester transfer protein -- CIRM California institute for regenerative medicine -- CNV choroidal neovascularization -- DHR delayed hyperacute rejection -- EDTA ethylenediaminetetraacetic acid -- ERG electroretinography -- GA geographic atrophy -- GMP good manufacturing practices -- GWAS genome wide association study -- HAR hyperacute rejection -- HRTA1 high temperature required factor A1 -- HuCNS-SC Human Central Nervous System Stem Cell -- hESC human embryonic stem cell -- IL interleukin -- IFNγ interferon gamma -- iPSC induced pluripotent stem cell -- iPSC-RPE induced pluripotent stem cell-derived retinal pigment epithelium -- KSR knock down serum replacement -- LipC lipase C -- LPCB London project to cure blindness -- LPS lipopolysaccharide -- MHC major histocompatibility complex -- MLR mixed lymphocyte reaction -- MSC mesenchymal stem cell -- NIC nicotinamide -- NV-AMD neovascular age-related macular degeneration -- NNV-AMD non-neovascular age-related macular degeneration -- OCT optical coherence tomography -- OHT optokinetic head tracking -- PBMC peripheral blood mononuclear cell -- PEDF pigment epithelium derived factor -- RPC retinal progenitor cell -- PR photoreceptor -- RPE retinal pigment epithelium -- SC stem cell -- SOD standard operating procedure -- RCS rat Royal College of Surgeons' rat -- RPC retinal progenitor cell -- TGF transforming growth factor -- Treg regulatory T lymphocyte -- hUTC human umbilical tissue-derived cells -- VEGF vascular endothelial growth factor; Retina -- Periodicals; Retina -- Research -- Methodology -- Periodicals; Eye -- Diseases -- Periodicals; Eye -- Periodicals; Eye Diseases -- Periodicals; Retina -- Periodicals; Rétine -- Périodiques; Rétine -- Recherche -- Méthodologie -- Périodiques; 617.7005
• DOI: 10.1016/j.preteyeres.2015.06.004
• Languages: English
• ISSNs: 1350-9462

Abstract

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.