April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
TP53 Gene Modulates Astroglial Cell Cycle and Nitric Oxide Synthesis in the Mouse Retina
Author Affiliations & Notes
  • M. D. Pinazo-Duran
    Ophthalmic Research Unit, Santiago Grisolia, Valencia, Spain
  • R. Gallego-Pinazo
    Ophthalmic Research Unit, Santiago Grisolia, Valencia, Spain
    Ophthalmology, University Hospital La Fe, Valencia, Spain
  • A. I. Ramirez-Sebastián
    Ophthalmic Research Institute, Ramon Castroviejo, Universidad Complutense de Madrid, Spain
  • J. J. Salazar
    Ophthalmic Research Institute, Ramon Castroviejo, Universidad Complutense de Madrid, Spain
  • J. M. Ramirez-Sebastián
    Ophthalmic Research Institute, Ramon Castroviejo, Universidad Complutense de Madrid, Spain
  • V. C. Zanón-Moreno
    Ophthalmic Research Unit, Santiago Grisolia, Valencia, Spain
  • V. Andrés
    Cell Biology, Biomedical Institute, Consejo Sup Investigaciones Cientificas Valencia, Spain
  • Footnotes
    Commercial Relationships  M.D. Pinazo-Duran, None; R. Gallego-Pinazo, None; A.I. Ramirez-Sebastián, None; J.J. Salazar, None; J.M. Ramirez-Sebastián, None; V.C. Zanón-Moreno, None; V. Andrés, None.
  • Footnotes
    Support  Grant PI061862 (Instituto Salud Carlos III-FIS) Glaucoma Prevention,
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2145. doi:
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      M. D. Pinazo-Duran, R. Gallego-Pinazo, A. I. Ramirez-Sebastián, J. J. Salazar, J. M. Ramirez-Sebastián, V. C. Zanón-Moreno, V. Andrés; TP53 Gene Modulates Astroglial Cell Cycle and Nitric Oxide Synthesis in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2145.

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Abstract

Purpose: : To determine the influence of TP53 gene in the retinal astroglia morphology and function.

Methods: : Adult mice of the strain C57BL/6 were distributed into two groups: 1) wild type TP53, as the controls (cp53; n=20) and 2) mice with an extra copy of TP53 (sp53; n=22). Both eyeballs were enucleated, after death by ether narcosis, to obtain the retinas. Right retinas were frozen (-85ºC) until processing to assess nitric oxide (NO) synthesis. Left retinas were obtained and proccesed to perform immunohistochemical localization of the glial fibrillary acidic protein (GFAP). Data are expressed as the mean ± SD. Statistical analysis was carried out using Student’s t-test. Confidence interval was taken at 95%.

Results: : The NO levels were significantly higher in the sp53 retinas than in the cp53 ones (145 + 15 vs 111 + 10 µM; p<0,05). Strong GFAP expression was detected and mapped by fluorescence microscopy in the whole retinas. GFAP+ stellate cells were located throughout the peripheral, equatorial and central retina. Astroglial density was significantly higher in the sp53 retinas as compared to the cp53 group (72 + 8 vs 49 + 6 cells/retinal area; p<0,001).

Conclusions: : Our paradigms suggest a complex set of TP53 regulatory actions: 1) to modulate NO production (probably recruiting a latent retinal astrocytic population), 2) to regulate the sensitivity toward NO in the retina by protecting astrocytes from oxidative attack. Increasing p53 activity may be an outstanding therapeutic strategy for certain retinal diseases.

Keywords: retina • astrocyte • nitric oxide 
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