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C. Jaillard, A. Mouret, Y. Yang, E. Clérin, B. Kinzel, J. Bennett, P. Lledo, J. Sahel, T. Léveillard; Impaired Vision and Olfaction in Mice Lacking RdCVF2. Invest. Ophthalmol. Vis. Sci. 2009;50(13):491.
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© ARVO (1962-2015); The Authors (2016-present)
We have reported the bioinformatic identification of RdCVF2, a second trophic factor belonging to the Rod-derived ConeViability Factor (RdCVF) family. RdCVF2 like RdCVF is secreted by rods and promote cone viability in mouse model of disease.
We analysed RdCVF2 expression in the retina and outside of retina by in situ hybridization. Next, we characterized the phenotype of RdCVF2 knockout mice. The visual function of the RdCVF2 -/- mice has been tested by electroretinography. We used in vitro olfactory neurons to quantify effects of RdCVF2 on olfactory neurons survival. To explore olfactory function in RdCVF2-/-, we performed some olfactory discrimination learning tests.
RdCVF2 mRNA was found to be expressed in the retina and in the olfactory epithelium. The postnatal development of retinal photoreceptors in the RdCVF2-/- mice was indistinguishable from that of wild-type (wt) controls as judged by histology and electroretinograms (ERGs) in younger mice. By 10 months of age, 30% of cones were lost. Along with the loss of cones, ERG amplitudes declined compared of wt controls. This phenotype was restored by AAVRdCVF2 injection in RdCVF2-/- at 6 months of age. Since RdCVF2 mRNA was detected in olfactory neurons, we analysed possible viability activity of RdCVF2 on adult culture of olfactory neurons. The cultures were made in the presence or absence of RdCVF2. The olfactory neurons were found to survive to higher rate when cultured in the presence of RdCVF2. To explore olfactory function in RdCVF2-/- compared to control mice, we performed olfactory discrimination learning tests. At 2 months of age, RdCVF2-/- mice showed correct responses are similar to those of wt mice. However, by 12 months of age the RdCVF2-/- mice failed to respond correctly to the stimulus.
Our results support the extension of the RdCVF2 signalling outside the eye. RdCVF2 as demonstrated in vitro and in vivo would be a potential therapy for degeneration on the nervous system.
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