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Pierre-Paul Elena, Sophie Antonelli, Virginie Mauro, Cimbolini Nicolas, Thomas Lamonerie, Laurence Feraille; Conditional self-knockout of otx2 mice: a new model for late-onset neuronal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4532. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The major cause of adult blindness is the progressive dysfunction and death of retinal photoreceptors (PR). In some inherited retinal degeneration, mutation in retinal pigment epithelium (RPE) appears to be the initial site of pathogenesis. In the mature retina, otx2, a transcription factor, is strongly expressed and implicated in RPE function integrity. The purpose of the study was to confirm that conditional otx2 self-knockout induced RPE dystrophy and photoreceptor degeneration in mouse and this model could be used as a new model for late-onset neuronal degeneration.
Conditional self-knockout of otx2 was induced by tamoxifen injection in Otx2CreERT2/flox mice. The mice Otx2CreERT2/flox and wild type (129Sv) were examined from P30 (induction) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemistry To investigate functional consequences of otx2 ablation, we performed electroretinography.
En face imaging in otx2 and wild type mice 3 weeks after tamoxifen treatment failed to detect signs of retinal degeneration. In contrast, cross-sectional images SD-OCT imaging showed a complete lack of outer and inner segments (OS/IS) in Otx2CreERT2/flox with ONL-OS/IS thickness of 57 ± 2.0 µm (mean ± SD, n=10) in comparison with wild type, 93.8 ± 2.0 µm. Scotopic and photopic ERG recordings revealed a decrease of rod and cone response after otx2 ablation. Histology confirmed the loss of OS/IS.
The study showed that otx2 ablation in adult retina induced a photoreceptor degeneration. This photoreceptor degeneration is related to RPE dysfunction (Housset, 2013) providing a new model for late-onset neuronal degeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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