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Reinnervation of Central Visual Areas and Recovery of Visual Functions Following Optic Nerve Regeneration in Adult Mice Yoshiki Koriyama 1,2,3 , Takuji Kurimoto 2,3,4 , Silmara de Lima 2,3,5 , Larry Benowitz 2,3 1Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University 2Laboratories for Neuroscience Research in Neurosurgery and F.M. Kirby Neurobiology Center, Children's Hospital, Boston 3Departments of Surgery and Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA 4Department of Ophthalmology, Osaka Medical College 5Program of Basic and Clinical Neuroscience, Institute of Biomedical Sciences, Centre of Health Sciences, Universidade Federal do, Rio de Janeiro, Brazil Keyword: 中枢神経再生 , オンコモジュリン , 網膜 , 神経回路形成 , 視覚 , regeneration , oncomodulin , retina , pathfinding , vision pp.265-272
Published Date 2014/3/1
DOI https://doi.org/10.11477/mf.1416101740
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Abstract

The optic nerve has been widely studied in search for insights into mechanisms that suppress or promote axon regeneration after injury. Like other CNS neurons, adult retinal ganglion cells (RGCs) normally fail to regenerate their axons after optic nerve injury. Recent studies have identified molecular pathways able to allow partial regeneration of damaged RGCs axons in mature rodents; however, it is still unknown, whether regrowing optic axons can re-enter the brain in large numbers, innervate the correct target areas, and thus restore vision. We investigated these questions by using three manipulations that synergistically increase regeneration far above the level induced by any of the three used alone. Oncomodulin is a calcium-binding protein secreted by activated macrophages and neutrophils and stimulates RGCs to regenerate axons. Its ability to bind to RGCs and activate a downstream response is enhanced by elevating intracellular cAMP. Studies were carried out in mice with a conditional deletion of the gene encoding PTEN, a phosphatase and tensin homolog that suppresses signaling through the Akt/mTOR/S6K pathway. Our results showed that intraocular inflammation, deletion of the PTEN gene and elevation of intracellular cAMP exert synergistic effects that enable RGCs to regenerate the full length of axons, form synapses, and restore simple visual functions. These results demonstrate the feasibility of reconstructing central circuitry for vision after optic nerve damage in mature mammals. (Receieved July 3, 2013; Accepted October 2, 2013; Published March 1, 2014)


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電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院

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