Abstract
Purpose: :
Nitric oxide (NO), a diffusible short-lived molecule displays a variety of biological activities including vasorelaxation and neurotransmission. Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic molecule. The p53 gene, an angiogenesis/apoptosis regulator, may be involved in the pathogenesis of age-related macular degeneration (ARMD) or primary open-angle glaucoma (POAG).
Methods: :
Adult mice of the C57BL/6 strain were distributed into two groups: 1) wild type p53 mice used as controls (cp53; n=24) and 2) transgenic mice with two more copies of p53 (sp53; n=20). Eyeballs were enucleated after death in CO2 athmosphere, microdissected to obtain the whole retina, and processed to immunohistochemistry by using a glial fibrilary acidic protein (GFAP) monoclonal antibody. Other eyes were freshly micro-dissected to obtain and frozen the retina-choroid, to assess both the NO and VEGF expression. Data were statistically processed by SPSS 15.0 program. Confidence interval was taken at 95%.
Results: :
Strong GFAP expression in whole retinas was detected and mapped by fluorescence microscopy. Density of GFAP+ astrocytes was significantly higher in the sp53 than in the cp53 retinas (72+8 vs 49+6 cells/retina; p<0,001). The NO and VEGF expressions were noticeably increased in the sp53 retina-choroid than in the cp53 ones.
Conclusions: :
Retinal astrocytes cooperate in the pathological retinal vascular responses, via NO and VEGF, in relation to p53 availability. Molecular strategies by enhancing endogenous p53 function in the eyes are expected to improve the prognosis of ocular diseases as the ARMD or POAG.
Keywords: retina • astrocyte • nitric oxide