BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice.
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 Miller 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 Müller 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.
Zencak
Dusan
D
Unit of Oculogenetics, Jules Gonin Eye Hospital, Lausanne, Switzerland.
Crippa
Sylvain V
SV
Tekaya
Meriem
M
Tanger
Ellen
E
Schorderet
Daniel E
DE
Munier
Francis L
FL
van Lohuizen
Maarten
M
Arsenijevic
Yvan
Y
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004596:Electroretinography; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
C069077:BMI1 protein, human; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1