■弓形虫病影响世界人口的三分之一,并以原生动物弓形虫为病原体。先天性弓形虫病(CT)可对胎儿造成严重损害,包括流产,颅内钙化,脑积水和视网膜脉络炎。CT的严重程度取决于发生感染的妊娠期,并且已经报道了视网膜发育过程中细胞水平的改变。在这项研究中,我们提出了一种小鼠CT模型来研究感染对视网膜发育的影响。
■在胚胎第10天(E10),用两个弓形虫囊肿(ME49株)对色素C57BL/6品系小鼠的怀孕雌性进行胃内感染,并在E18分析后代。
■受感染的胚胎的体型和体重明显小于PBS处理的对照组,表明胚胎发育受到影响。在视网膜上,与对照组相比,在感染小鼠的NBL顶端区域发现Ki-67阳性细胞(增殖细胞标志物)数量显著增加.支持这一点,细胞周期蛋白CyclinD3,Cdk6和pChK2在感染的视网膜中发生显着变化。有趣的是,免疫组织化学分析显示β-III-微管蛋白阳性细胞的数量显着增加,神经元分化的最早标志之一。
■我们的数据表明CT影响视网膜祖细胞的细胞周期进程,可能诱导这些细胞停滞在G2/M期。这种改变可能会影响分化,预测/增加神经元成熟,从而导致异常的视网膜形成。我们的模型模拟了眼CT中观察到的重要事件。
UNASSIGNED: Toxoplasmosis affects one third of the world population and has the protozoan Toxoplasma gondii as etiological agent. Congenital toxoplasmosis (CT) can cause severe damage to the fetus, including miscarriages, intracranial calcification, hydrocephalus and retinochoroiditis. Severity of CT depends on the gestational period in which infection occurs, and alterations at the cellular level during retinal development have been reported. In this study, we proposed a mouse CT model to investigate the impact of infection on retinal development.
UNASSIGNED: Pregnant females of pigmented C57BL/6 strain mice were infected intragastrically with two T. gondii cysts (ME49 strain) at embryonic day 10 (E10), and the offspring were analyzed at E18.
UNASSIGNED: Infected embryos had significantly smaller body sizes and weights than the PBS-treated controls, indicating that embryonic development was affected. In the retina, a significant increase in the number of Ki-67-positive cells (marker of proliferating cells) was found in the apical region of the NBL of infected mice compared to the control. Supporting this, cell cycle proteins Cyclin D3, Cdk6 and pChK2 were significantly altered in infected retinas. Interestingly, the immunohistochemical analysis showed a significant increase in the population of β-III-tubulin-positive cells, one of the earliest markers of neuronal differentiation.
UNASSIGNED: Our data suggests that CT affects cell cycle progression in retinal progenitor cells, possibly inducing the arrest of these cells at G2/M phase. Such alterations could influence the differentiation, anticipating/increasing neuronal maturation, and therefore leading to abnormal retinal formation. Our model mimics important events observed in ocular CT.