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  • BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice

    Author(s)
    Zencak, Dusan
    V. Crippa, Sylvain
    Tekaya, Meriem
    Tanger, Ellen
    F. Schorderet, Daniel
    L. Munier, Francis
    van Lohuizen, Maarten
    Arsenijevic, Yvan
    Griffith University Author(s)
    Zencak, Dusan
    Year published
    2006
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    Abstract
    Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1 -/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal M쬬er glia as a source of neural ...
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    Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1 -/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal M쬬er glia as a source of neural protection in the retina, the increased astrocytic population in the Bmi1 -/- brain led us to investigate the effect of Bmi1 loss in Rd1 mice. We observed an increase of M쬬er glial cells in Rd1-Bmi1 -/- retinas compared to Rd1. Moreover, Rd1-Bmi1 -/- mice showed 7-8 rows of photoreceptors at 30 days of age (P30), while in Rd1 littermates there was a complete disruption of the outer nuclear layer (ONL). Preliminary ERG results showed a responsiveness of Rd1-Bmi1 -/- mice in scotopic vision at P35. In conclusion, Bmi1 loss prevented, or rescued, photoreceptors from degeneration to an unanticipated extent in Rd1 mice. In this chapter, we will first provide a brief review of our work on the cortical NSCs and introduce the Bmi1 oncogene, thus offering a rational to our observations on the retina.
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    Book Title
    Retinal Degenerative Diseases
    Publisher URI
    http://dx.doi.org/10.1007/0-387-32442-9
    DOI
    https://doi.org/10.1007/0-387-32442-9_31
    Subject
    Cell Development, Proliferation and Death
    Publication URI
    http://hdl.handle.net/10072/63670
    Collection
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