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F. R. Vazquez-Chona, A. Swan, D. M. Defoe, E. M. Levine; Conditional p27 Inactivation in the Adult Mouse Induces Muller Glial Reactivity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2150.
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Muller glia support the survival of photoreceptors and in some species Muller glia regenerate photoreceptors. In humans, the metabolic demands of retinal degenerations can over-activate Muller glia into a "reactive" state where they become hypertrophic, migratory and mitotic. We are testing the hypothesis that the cell-cycle inhibitor p27KIP1 is a negative regulator of Muller glial reactivity.
To test our hypothesis we used a conditional gene targeting approach. We inactivated p27 in adult Muller glia using the floxed p27 x Actin:CreER line. Classic signaling pathways of glial reactivity and metabolic states of Muller glia were assayed using conventional protein profiling (immunohistochemistry and Western blots) and metabolic profiling (computational molecular phenotyping, CMP).
Global conditional inactivation of p27 results in Muller glial reactive behavior: (i) upregulation of cytoskeletal proteins including GFAP and VIM; (ii) Muller glial endfeet into the photoreceptor segments; and (iii) focal disruption of the outer limiting membrane.
These data provide evidence that p27 inactivation in adult mice is sufficient to promote reactivity in Muller glia, which supports our hypothesis that p27 is a negative regulator of this behavior.
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