title: DNA repair in the degenerating mouse retina.
abstract: In light of different recent results suggesting that the adult mammalian central nervous system can produce new neurons, possibly as an endogenous repair mechanism, we investigated whether neurogenesis occurs in response to photoreceptor degeneration in the rd1 mouse, a model of human-inherited retinal dystrophy. Bromodeoxy-Uridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression experiments detected cell proliferation in the extreme peripheral retina, in both wt and rd1 retina, independent of degeneration. BrdU incorporation and PCNA expression also occurred in rd1 photoreceptors. Our results strongly suggest that these photoreceptors undergo DNA repair: p53, PCNA, and DNA ligase IV are expressed before photoreceptor death, consistent with a model where photoreceptors expressing the rd1 mutation activate a process of DNA repair but which is overwhelmed by the disease mutation leading to apoptotic death. The existence of such a balance offers potential new targets for neuroprotective approaches.
authors.affiliation: Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine, INSERM U 592 Université Pierre et Marie Curie, Hôpital Saint-Antoine, Bâtiment Kourilsky, 75571 Paris Cedex 12, France.
authors.forename: L
authors.initials: L
authors.lastname: Menu dit Huart
authors.forename: O
authors.initials: O
authors.lastname: Lorentz
authors.forename: O
authors.initials: O
authors.lastname: Goureau
authors.forename: T
authors.initials: T
authors.lastname: Léveillard
authors.forename: J A
authors.initials: JA
authors.lastname: Sahel
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004260:DNA Repair; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*