Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma |
| |
| Affiliation: | 1. Molecular and Cellular Biomedicine, School of Medical Sciences, The University of Sydney, NSW, Australia;2. Save Sight Institute, The University of Sydney, NSW, Australia;1. Pediatric Vision Laboratory, Retina Foundation of the Southwest, 9600 North Central Expressway #200, Dallas, TX, 75225, USA;2. Department of Ophthalmology, University of Texas Southwestern Medical Center, 5303 Harry Hines Boulevard, Dallas, TX, 75390, USA;3. Vision and Neurodevelopment Laboratory, Retina Foundation of the Southwest, 9600 North Central Expressway #200, Dallas, TX, 75225, USA;1. Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, CA, USA;2. International Center for Translational Eye Research, Polish Academy of Sciences, Warsaw, Poland;3. Polgenix, Inc., Department of Medical Devices, Cleveland, OH, USA;4. Department of Physical Chemistry of Biological Systems, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland;5. Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Torun, Poland;6. Department of Physiology & Biophysics, School of Medicine, And Chemistry, Molecular Biology and Biochemistry, University of California, Irvine, CA, USA;1. Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France;2. Paris-Saclay Institute of Neuroscience, CERTO-Retina France, CNRS, Université Paris-Saclay, Saclay, France;3. CHNO des Quinze-Vingts, INSERM-DGOS CIC 1423, Paris, France;4. Service of Biochemistry and Molecular Biology, INSERM U942, Hospital Lariboisière, APHP, Paris, France;5. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON, Canada;6. Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada;7. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada;8. Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;9. Department of Biology, ETH Zurich, Zurich, Switzerland;10. Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR, USA;11. Oujiang Laboratory, Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health, Wenzhou, China;12. Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University, New York, NY, USA |
| |
| Abstract: | Elevation of intraocular pressure (IOP) is a major risk factor for neurodegeneration in glaucoma. Glial cells, which play an important role in normal functioning of retinal neurons, are well involved into retinal ganglion cell (RGC) degeneration in experimental glaucoma animal models generated by elevated IOP. In response to elevated IOP, mGluR I is first activated and Kir4.1 channels are subsequently inhibited, which leads to the activation of Müller cells. Müller cell activation is followed by a complex process, including proliferation, release of inflammatory and growth factors (gliosis). Gliosis is further regulated by several factors. Activated Müller cells contribute to RGC degeneration through generating glutamate receptor-mediated excitotoxicity, releasing cytotoxic factors and inducing microglia activation. Elevated IOP activates microglia, and following morphological and functional changes, these cells, as resident immune cells in the retina, show adaptive immune responses, including an enhanced release of pro-inflammatory factors (tumor neurosis factor-α, interleukins, etc.). These ATP and Toll-like receptor-mediated responses are further regulated by heat shock proteins, CD200R, chemokine receptors, and metabotropic purinergic receptors, may aggravate RGC loss. In the optic nerve head, astrogliosis is initiated and regulated by a complex reaction process, including purines, transmitters, chemokines, growth factors and cytokines, which contributes to RGC axon injury through releasing pro-inflammatory factors and changing extracellular matrix in glaucoma. The effects of activated glial cells on RGCs are further modified by the interplay among different types of glial cells. This review is concluded by presenting an in-depth discussion of possible research directions in this field in the future. |
| |
| Keywords: | Glaucoma Müller cells Microglia Astrocyte Activation Retinal ganglion cell degeneration |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
