title: Optic nerve lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo.
abstract: In the naïve adult rodent eye cell proliferation does not occur. The aim of this in vivo study was to evaluate if quiescent putative progenitor-like cells within the adult mouse eye can be activated by optic nerve (ON) injury. For a comprehensive analysis, three areas were assessed: the ON, the neural retina, and the ciliary body (CB). Two lesion types were performed, i.e. intraorbital ON transection, or ON crush lesion, in order to analyse possible differences in cellular response after injury. This mouse study shows, for the first time that ON lesion up-regulates cell proliferation and nestin expression in the mouse eye as compared to naïve controls. Numbers and distribution patterns of BrdU+ cells obtained were similar after both lesion types, suggesting analogous mechanisms of activation. Interestingly, a differential cell proliferative response was observed in the CB. After ON lesion, the absence of BrdU/TUNEL co-labelled cells confirmed that BrdU+ cells were indeed proliferating. Following ON lesion, in the retina approximately 18% of all BrdU+ cells were positive for the neural stem cell/progenitor cell (NSC/PC) marker nestin. The fraction of BrdU+/nestin+ cells in the CB was approximately 26%. Most of the BrdU+/nestin+ cells found in the neural retina were identified as reactive astrocytes and Müller cells. Since reactive glia cells can participate in adult neuro- and gliogenesis this may indicate a potential for regeneration after ON lesion in vivo.
authors.affiliation: Department of Experimental Neurology, University of Jena Medical School, Erlanger Allee 101, 07747 Jena, Germany. stefanie.wohl@med.uni-jena.de
authors.forename: Stefanie G
authors.initials: SG
authors.lastname: Wohl
authors.forename: Christian W
authors.initials: CW
authors.lastname: Schmeer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kretz
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.forename: Stefan
authors.initials: S
authors.lastname: Isenmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D001973:Bromodeoxyuridine