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Y. Arsenijevic, D. Zencak, S.V. Crippa, M. Tekaya, E. Tanger, D.F. Schorderet, M. van Lohuizen, F.L. Munier; Loss of Bmi1 Prevents Degeneration of Photoreceptors in rd Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2298.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinitis pigmentosa (RP) is a major cause of blindness and remains practically untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the progression of the disease in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell renewal in the brain, and a strong increase in glial cells was detected in vivo in the brain of Bmi1 knockout (Bmi1–/–) mice. Considering the role of Müller cells, a retinal glial cell, as a possible source of neural protection in the retina, we investigated the effect of Bmi1 loss in rd mice. Methods: We compared the histology of Rd1–Bmi1+/+, +/– and Rd1–Bmi1–/– eyes at birth and at 30 days of age (P30) by performing immunohistochemical stainings to analyze the different retinal cell classes, proliferation (by BrdU incorporation) and apoptosis (by TUNEL). ERG in Rd1–Bmi1–/– and control (Rd1–Bmi1+/+ or +/–) mice was tested in scotopic and photopic conditions at different ages ranging from P16 to P35. Results: We observed an increase of immunoreactivity for CRALBP, a Müller glia marker, in Rd1–Bmi1–/– retinas compared to Rd1–Bmi1+/+. Moreover, Rd1–Bmi1–/– mice showed 7–8 rows of photoreceptors at P30, while in Rd1–Bmi1+/+ rd littermates there was a complete atrophy of the outer nuclear layer (ONL) already at P21. Most interestingly, the photoreceptors present in the P30 Rd1–Bmi1–/– retina were positive for rod photoreceptor markers such as recoverin and rhodopsin, with long outer segments, and ERG recordings showed a responsiveness in all Rd1–Bmi1–/– mice investigated in scotopic condition from P15 to P35. Conclusions: : Bmi1 loss prevented photoreceptor degeneration to an unanticipated extent in Rd1 mice. The rescued photoreceptors had a rod phenotype and were functional, as assessed by ERG recordings.
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