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Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies.
Prog Retin Eye Res. 2021 Apr 28 [Online ahead of print]PR

Abstract

Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Müller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Müller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Müller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Müller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Müller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Müller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Müller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases.

Authors+Show Affiliations

NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. Electronic address: g.limb@ucl.ac.uk.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33930561

Citation

Eastlake, K, et al. "Prospects for the Application of Müller Glia and Their Derivatives in Retinal Regenerative Therapies." Progress in Retinal and Eye Research, 2021, p. 100970.
Eastlake K, Lamb WDB, Luis J, et al. Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies. Prog Retin Eye Res. 2021.
Eastlake, K., Lamb, W. D. B., Luis, J., Khaw, P. T., Jayaram, H., & Limb, G. A. (2021). Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies. Progress in Retinal and Eye Research, 100970. https://doi.org/10.1016/j.preteyeres.2021.100970
Eastlake K, et al. Prospects for the Application of Müller Glia and Their Derivatives in Retinal Regenerative Therapies. Prog Retin Eye Res. 2021 Apr 28;100970. PubMed PMID: 33930561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies. AU - Eastlake,K, AU - Lamb,W D B, AU - Luis,J, AU - Khaw,P T, AU - Jayaram,H, AU - Limb,G A, Y1 - 2021/04/28/ PY - 2020/10/15/received PY - 2021/03/28/revised PY - 2021/03/31/accepted PY - 2021/5/1/pubmed PY - 2021/5/1/medline PY - 2021/4/30/entrez KW - Müller glia KW - Neural retina KW - Neuroprotection KW - Regeneration KW - Stem cells SP - 100970 EP - 100970 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Müller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Müller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Müller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Müller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Müller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Müller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Müller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/33930561/Prospects_for_the_application_of_Müller_glia_and_their_derivatives_in_retinal_regenerative_therapies. L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(21)00031-8 DB - PRIME DP - Unbound Medicine ER -
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