Smith Christopher P, Steinle Jena J
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
Exp Eye Res. 2007 Dec;85(6):817-24. doi: 10.1016/j.exer.2007.08.017. Epub 2007 Aug 29.
Although much is known about the growth factor changes in ocular tissues during various diseases, little is known about normal aging of the retina. In order to further understand normal aging in the retina, we characterized age-related changes of growth factor expression in three different ages of rat retina. Real time PCR and protein analysis was conducted to investigate steady state mRNA expression and protein levels of VEGF, VEGFR2, PEDF, Ang-1, Tie-2, EphB4 and ephrinB2 in the retina of 8-, 22-, and 32-month-old Brown Norway X Fischer 344 F1 hybrid rats. An increase of VEGF protein levels was found at 32months compared to 8 and 22months of age. VEGFR2 protein was found to be increased at 22 and 32months compared to 8months. PEDF protein levels were reduced at 22 and 32months. Tie-2 levels were found to be significantly decreased by 32months compared to 8months of age, while ephrinB2 was found to be significantly lower at both 22 and 32months compared to 8months of age. The increases found in VEGF and its receptor VEGFR2, with the simultaneous decrease of PEDF protein levels, may stimulate an environment that is well suited for neovascularization in the normal aging retina. Overall, these results suggest that normal aging produces substantial changes in gene expression and protein levels.
尽管我们对各种疾病期间眼组织中生长因子的变化了解很多,但对视网膜的正常老化却知之甚少。为了进一步了解视网膜的正常老化过程,我们对三种不同年龄大鼠视网膜中生长因子表达的年龄相关变化进行了特征分析。采用实时定量PCR和蛋白质分析方法,研究了8月龄、22月龄和32月龄的棕色挪威大鼠与费希尔344大鼠杂交F1代大鼠视网膜中血管内皮生长因子(VEGF)、血管内皮生长因子受体2(VEGFR2)、色素上皮衍生因子(PEDF)、血管生成素-1(Ang-1)、酪氨酸激酶受体2(Tie-2)、 EphB4和ephrinB2的稳态mRNA表达和蛋白质水平。结果发现,与8月龄和22月龄相比,32月龄大鼠的VEGF蛋白水平升高。与8月龄相比,22月龄和32月龄大鼠的VEGFR2蛋白水平升高。22月龄和32月龄大鼠的PEDF蛋白水平降低。与8月龄相比,32月龄大鼠的Tie-2水平显著降低,而与8月龄相比,22月龄和32月龄大鼠的ephrinB2水平均显著降低。VEGF及其受体VEGFR2的增加,同时PEDF蛋白水平的降低,可能会刺激正常老化视网膜中适合新生血管形成的环境。总体而言,这些结果表明正常老化会导致基因表达和蛋白质水平发生显著变化。