title: Otx2 promotes the survival of damaged adult retinal ganglion cells and protects against excitotoxic loss of visual acuity in vivo.
abstract: Retinal ganglion cells (RGCs) are the projection neurons from the eye to the brain and their loss results in visual impairment in a number of diseases. Transcription factors with a homeodomain can translocate between cells and, in at least one reported case, can stimulate neuronal survival. Otx2 is a homeoprotein transcription factor expressed in the retina that is taken up by RGCs. We thus hypothesized that Otx2 capture could regulate the survival of adult RGCs. We report that Otx2 stimulates the survival of adult mouse and rat RGCs in vitro and protects RGCs against NMDA-induced toxicity in vivo in mice. In the latter model, Otx2 also preserves visual acuity.
authors.affiliation: Centre for Interdisciplinary Research in Biology, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale Unité 1050, Collège de France and Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Torero Ibad
authors.forename: Jinguen
authors.initials: J
authors.lastname: Rheey
authors.forename: Sarah
authors.initials: S
authors.lastname: Mrejen
authors.forename: Valérie
authors.initials: V
authors.lastname: Forster
authors.forename: Serge
authors.initials: S
authors.lastname: Picaud
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Moya
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000633:toxicity; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D009842:Oligopeptides / Q000494:pharmacology; D009907:Optometry / Q000379:methods; D051857:Otx Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000378:metabolism; D014792:Visual Acuity / Q000187:drug effects* / Q000502:physiology
chemical_list: C485182:Cyan Fluorescent Protein; D004791:Enzyme Inhibitors; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009842:Oligopeptides; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D012333:RNA, Messenger; D050819:Transcription Factor Brn-3A; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C051774:neurofilament protein H; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate