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christel Masson-Garcia, Annaïg HAMON, Juliette Bitard, Jerome E Roger, Muriel PERRON; Retinal degeneration triggers the activation of the Hippo pathway effector gene YAP in reactive Müller cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4201.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations leading to blindness and currently untreatable. In these diseases, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, which has both beneficial and detrimental effects on cell survival. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of promising new therapeutic strategies. To identify novel players acting in Müller glia neuroprotective response, we focused our interest on the Hippo pathway, a key regulator of tissue homeostasis.
We used rd10 mice (Pde6Brd10/rd10) as a model of human RP. These mice carry a mutation of the rod-specific phosphodiesterase gene and undergo rod death from P16. We determined mRNA and protein levels of Hippo/Yap pathway components using a combination of quantitative real-time PCR, Western blot, and immunohistochemistry
In wild-type postnatal and adult mice, we found that the effectors of the Hippo pathway, YAP1 and TEAD1, are specifically expressed in Müller cells. A comparison of their mRNA and protein levels between wild type and rd10 mice retina revealed an upregulation associated with photoreceptor loss. To determine the transcriptional outcome of this regulation of the Hippo pathway, we examined the expression of YAP1/TEAD1 well known target gene Cyr61 and found a 4-fold increase in rd10 retinas compared to control ones
This work uncovers a link between the Hippo/YAP pathway and Müller cell-dependent response to photoreceptor loss. Given the Müller cell mediated pro-survival capacities recently reported for Cyr61 (Kucharska et al., Journal of Neurochemistry 2014), our work also suggests that the activation of YAP1/TEAD1 activity in reactive Müller glia may be involved in a mechanism promoting photoreceptor neuroprotection in the degenerating retina.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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