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Ling Zhu, Weiyong Shen, Ying Wang, Ting Zhang, Bobak Bahrami, Fanfan Zhou, Mark C Gillies; Characterization of canonical Wnt signalling changes after induced Müller cell disruption in murine retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):611.
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© ARVO (1962-2015); The Authors (2016-present)
Müller cells are the principal retinal glial cell, providing homeostatic and metabolic support for the neurons of the vertebrate retina. The canonical Wnt signalling pathway also plays an important role in maintaining homeostasis in the retina. Target genes activated by the Wnt pathway have a range of roles in retinal physiology and pathology. We aim to evaluate the Wnt signalling and its downstream effects on retinal degeneration in a transgenic model in which Müller cells were selectively and inducibly disrupted.
The retinal Wnt signaling activation after induced Muller cells disruption was detected by evaluating nuclear translocation of β-Catenin. The mRNA expression of 80 Wnt related genes was assessed by real-time PCR using the retinas from transgenic mouse and control mouse. The changes of these genes at protein level were further evaluated by Western blot. Their distributions in the retina were evaluated by immunohistochemistry.
Western blots of retinal lysates showed a significant up-regulation (207%, p=0.04) of nuclear β-catenin expression 7 days after induced Müller cell disruption compared with control. In the retinas of the mice induced Müller cell disruption, real-time PCR results showed significant down-regulations of Wnt inhibitors, sFRP3, Dkk1 and Dkk3 ( by 82%, 26% and 88% of control, respectively). Additionally, there were significant down-regulations of the β-Catenin proteolysis-related genes, βTrcp and SHFM3 ( by 70% and 56% of control, respectively). Furthermore, Wnt downstream target genes, Cyclin D2, C-Myc and Fra-1 were significantly up-regulated in the retina after induced Müller cell dysfunction (by 268%, 249% and 215% of control, respectively). We detected similar results of these genes’ changes at protein level by Western blot.
Our findings indicated that Müller cells are one of the major cell types involved in retinal Wnt signalling. Multiple cascades of retinal Wnt signalling were activated following Müller cell disruption. Activation of Wnt signalling and its downstream target genes may play important roles in photoreceptor degeneration and neovascularization occurring in the retina after induced Müller cell disruption.
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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