6533b85efe1ef96bd12c0562

RESEARCH PRODUCT

Nitric oxide synthesis is related to astroglial cell cycle in the mouse retina via p53 gene regulation

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Purpose To analyze the influence of p53 gene in retinal astrocytes 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 p53 (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). Conclusion All data suggest a complex set of p53 actions: 1) to regulate 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.