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K. Schwerdtfeger, C. Grimm, C. Remé, J. A. Fischer, W. Born, F. Hafezi; Retinal Cell Death and Pax6 Expression in a Transgenic Glaucoma Mouse Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4522.
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© ARVO (1962-2015); The Authors (2016-present)
Pax6 is a key regulatory factor during development of the eye. In the eye of adults Pax6 is still expressed in the inner retina, maybe due to remodelling for maintenance of regular morphology. Therefore, we investigated the Pax6 expression in a mouse model of retinal degeneration. These mice overexpress the Adrenomedullin (AM) receptor in smooth muscle cells (AMtg mice). This leads to glaucoma at 1 month of age, resulting in retinal degeneration.
Retinal morphology was analysed on semithin sections and retinal cell death was monitored by TUNEL assay. Pax6 expression levels were analysed by Western blotting and by immunofluorescence staining of retinal sections. The expression pattern of apoptosis related genes in the retina of AMtg mice and control littermates was studied by RT-PCR.
AMtg mice, unlike wild-type littermates, showed a progressive loss of cells in the retinal ganglion cell (RGC) layer between postnatal day (p) 22 and p82, while cell counts in the inner nuclear layer (INL) were unchanged. At p32 and p82 the apoptosis related genes: caspase-1, -11, -12, timp1, xiap, bcl-xl, bad, bcl-2, il-1ßand endothelin 2 showed significant changes in the retina of transgenic mice. Western blot analysis of retinal extracts showed a continuous decrease of PAX6 expression, except for p82 where a slight increase of PAX6 expression was observed. By morphometric analysis a loss of PAX6 positive cells was recognized in the RGC layer but not in the INL of transgenic animals. At time point p82 a distinct increase of PAX6 expression was detected in the INL of transgenic mice.
PAX6 expression in the inner retina is affected during retinal degeneration in AMtg mice. Furthermore, the shift of PAX6 expression from the RGC layer to the INL at p82 in AMtg mice might indicate crosstalk between different retinal cell layers.
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