title: [Reinnervation of central visual areas and recovery of visual functions following optic nerve regeneration in adult mice].
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.
authors.affiliation: Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Takuji
authors.initials: T
authors.lastname: Kurimoto
authors.forename: Silmara
authors.initials: S
authors.lastname: de Lima
authors.forename: Larry
authors.initials: L
authors.lastname: Benowitz
mesh_terms: D000375:Aging; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics; D009900:Optic Nerve / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014785:Vision, Ocular / Q000187:drug effects* / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; C034733:oncomodulin