State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Int J Mol Sci. 2018 Apr 17;19(4):1214. doi: 10.3390/ijms19041214.
Previous studies have reported that Brca1 acts as a “hinge” in the development of the central nervous system (CNS). However, the precise role of Brca1 in rat retinal neurons remains unclear. Here, we found that Brca1 is developmentally downregulated and silenced in adult retina. Brca1 was upregulated in rat primary retinal neurons by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment. Moreover, the upregulation of Brca1 by both 5-Aza-CdR and transgenic Brca1 promoted genomic stability and improved cell viability following exposure to ionizing radiation (IR). Furthermore, transgenic Brca1 significantly inhibited neurite outgrowth of retinal neurons, which implicates that Brca1 silencing promotes cell differentiation and determines neuronal morphology. Taken together, our results reveal a biological function of Brca1 in retinal development.
先前的研究报道称,Brca1 在中枢神经系统(CNS)的发育中充当“铰链”。然而,Brca1 在大鼠视网膜神经元中的确切作用仍不清楚。在这里,我们发现 Brca1 在成年视网膜中发育下调和沉默。5-Aza-2'-脱氧胞苷(5-Aza-CdR)处理可使大鼠原代视网膜神经元中 Brca1 上调。此外,5-Aza-CdR 和转基因 Brca1 的上调均可促进基因组稳定性,并提高电离辐射(IR)暴露后的细胞活力。此外,转基因 Brca1 显著抑制视网膜神经元的轴突生长,这表明 Brca1 沉默促进细胞分化并决定神经元形态。总之,我们的研究结果揭示了 Brca1 在视网膜发育中的生物学功能。