April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Conditional p27 Inactivation in the Adult Mouse Induces Muller Glial Reactivity
Author Affiliations & Notes
  • F. R. Vazquez-Chona
    Ophthalmology, Univ of Utah, Salt Lake City, Utah
  • A. Swan
    Ophthalmology, Univ of Utah, Salt Lake City, Utah
  • D. M. Defoe
    Anatomy and Cell Biology, East Tennessee State University, Johnson City, Tennessee
  • E. M. Levine
    Ophthalmology, Univ of Utah, Salt Lake City, Utah
  • Footnotes
    Commercial Relationships  F.R. Vazquez-Chona, None; A. Swan, None; D.M. Defoe, None; E.M. Levine, None.
  • Footnotes
    Support  NIH 5T32 HD07491, FFS PD07010, IRRF, R01 EY013760, FFB, and RPB
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2150. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : 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.

Methods: : 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).

Results: : 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.

Conclusions: : 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.

Keywords: retinal degenerations: cell biology • Muller cells • retinal glia 

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