Optic nerve lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo

• Published in: Experimental neurology 2009-09, Vol.219 (1), p.175-186
• Main Authors: Wohl, Stefanie G., Schmeer, Christian W., Kretz, Alexandra, Witte, Otto W., Isenmann, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Axotomy; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Bromodeoxyuridine; Cell Proliferation; Ciliary body; Crush; Disease Models, Animal; Female; Gliosis - metabolism; Gliosis - physiopathology; In Situ Nick-End Labeling; Injuries of the nervous system and the skull. Diseases due to physical agents; Intermediate Filament Proteins - metabolism; Intermediate filaments; Medical sciences; Mice; Mice, Inbred BALB C; Microglia; Müller glia; Nerve Regeneration - physiology; Nerve Tissue Proteins - metabolism; Nestin; Neurogenesis - physiology; Neurology; Optic Nerve Injuries - metabolism; Optic Nerve Injuries - pathology; Optic Nerve Injuries - physiopathology; Regeneration; Retina; Retina - metabolism; Retina - pathology; Retina - physiopathology; Stem Cells - cytology; Stem Cells - metabolism; Traumas. Diseases due to physical agents; TUNEL
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2009.05.008

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 ∼ 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 ∼ 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.