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D. Zencak, S.V. Crippa, M. Tekaya, D. Hornfeld, M. Jaquet, M. van Lohuizen, Y. Arsenijevic; Bmi1 Loss Affects the Development and the Function of Retinal Neurons . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2780.
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© ARVO (1962-2015); The Authors (2016-present)
Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell renewal in the brain, and it strongly affects brain morphogenesis, with a reduced brain size at late developmental stages, particularly accentuated in the cerebellum. Therefore, we sought to investigate the effects of Bmi1 loss in the retina, which continues to develop after birth.
We compared the function of the retina of Bmi1+/+ and Bmi1–/– mice on the C57/Bl6 background by performing electroretinogram (ERG) recordings between 22 (P22) and 30 (P30) days of age in scotopic and photopic conditions. To compare the general histology and the cellular composition of Bmi1+/+ and Bmi1–/– retinas, we performed several immunohistochemical stainings at P30 to analyze the different retinal cell classes.
ERG recordings showed an abnormal response to light stimuli in Bmi1–/– mice, characterized by reduced b–wave amplitudes, increased implicit times, and very poor oscillatory potentials at both P22 and P30, in scotopic and photopic conditions. We sought to correlate the ERG recordings with the histology of the Bmi1–/– retinas at P30, and found no obvious difference in the general structure of the retina (compared to Bmi1+/+), neither in the number or pattern of cone and rod photoreceptors, nor in ganglion cells, revealed respectively by GNAT2, Rho4D2, and NeuN staining. Müller glia appear to have a normal pattern, as revealed by CRALBP staining. However, we observed a decrease of 20% (p<0.01) in the number of horizontal cells as revealed by Calbindin labeling.
At this stage, our data show clearly that Bmi1 loss affects the development and the function of the retina. The decrease in horizontal cells suggests that retinal interneurons might play a leading role in the altered ERG response observed in Bmi1–/– mice. A deep histological, molecular and electrophysiological analysis is now in process to better understand the precise role of Bmi1 and to characterize the consequences of Bmi1 loss in retinal development and function.
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