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      Regenerative medicine in the retina: from stem cells to cell replacement therapy

      review-article
      ,
      Therapeutic Advances in Ophthalmology
      SAGE Publications
      cell replacement, cell therapy, stem cells, retina, glaucoma, AMD

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          Abstract

          Following the fast pace of the growing field of stem cell research, retinal cell replacement is finally emerging as a feasible mean to be explored for clinical application. Although neuroprotective treatments are able to slow the progression of retinal degeneration caused by diseases such as age-related macular degeneration and glaucoma, they are insufficient to fully halt disease progression and unable to recover previously lost vision. Comprehensive, technological and intellectual advances over the past years, including the in vitro differentiation of retinal cells at manufacturing scale from embryonic stem (ES) cell and induced pluripotent stem (iPS) cell cultures, progress within the area of retinal disease modeling, and the first clinical trials have started to shape the way towards addressing this treatment gap and translating retinal cell replacement to the clinic. Here, summarize the most recent advances within retinal cell replacement from both a scientific and clinical perspective, and discuss the remaining challenges towards the delivery of the first retinal cell products.

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          Most cited references136

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          The types of retinal ganglion cells: current status and implications for neuronal classification.

          In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that most RGCs are not merely light detectors, but rather feature detectors, which send a diverse set of parallel, highly processed images of the world on to higher centers. Here, we review progress in classification of RGCs by physiological, morphological, and molecular criteria, making a particular effort to distinguish those cell types that are definitive from those for which information is partial. We focus on the mouse, in which molecular and genetic methods are most advanced. We argue that there are around 30 RGC types and that we can now account for well over half of all RGCs. We also use RGCs to examine the general problem of neuronal classification, arguing that insights and methods from the retina can guide the classification enterprise in other brain regions.
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            Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling.

            In mammals, few retinal ganglion cells (RGCs) survive following axotomy, and even fewer regenerate axons. This could reflect differential extrinsic influences or the existence of subpopulations that vary in their responses to injury. We tested these alternatives by comparing responses of molecularly distinct subsets of mouse RGCs to axotomy. Survival rates varied dramatically among subtypes, with alpha-RGCs (αRGCs) surviving preferentially. Among survivors, αRGCs accounted for nearly all regeneration following downregulation of PTEN, which activates the mTOR pathway. αRGCs have uniquely high mTOR signaling levels among RGCs and also selectively express osteopontin (OPN) and receptors for the insulin-like growth factor 1 (IGF-1). Administration of OPN plus IGF-1 promotes regeneration as effectively as downregulation of PTEN; however, regeneration is still confined to αRGCs. Our results reveal dramatic subtype-specific differences in the ability of RGCs to survive and regenerate following injury, and they identify promising agents for promoting axonal regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.
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              Stimulation of functional neuronal regeneration from Müller glia in adult mice

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                Author and article information

                Contributors
                Journal
                Ther Adv Ophthalmol
                Ther Adv Ophthalmol
                OED
                spoed
                Therapeutic Advances in Ophthalmology
                SAGE Publications (Sage UK: London, England )
                2515-8414
                26 April 2018
                Jan-Dec 2018
                : 10
                : 2515841418774433
                Affiliations
                [1-2515841418774433]Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA
                [2-2515841418774433]Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, MA, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-5744-5500
                Article
                10.1177_2515841418774433
                10.1177/2515841418774433
                6016968
                29998222
                82b01828-b981-4031-a69e-4cc5461a1110
                © The Author(s), 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 19 October 2017
                : 15 February 2018
                Categories
                Review
                Custom metadata
                January-December 2018

                cell replacement,cell therapy,stem cells,retina,glaucoma,amd
                cell replacement, cell therapy, stem cells, retina, glaucoma, amd

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