Ethanol-induced microphthalmia is not mediated by changes in retinoic acid or sonic hedgehog signaling during retinal neurogenesis.
Ethanol-induced microphthalmia is not mediated by changes in retinoic acid or sonic hedgehog signaling during retinal neurogenesis.
复制标题
DOI：
10.1111/j.1530-0277.2011.01511.x
复制
发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Stenkamp DL
中科院分区：
文献类型：
--
作者：
Kashyap B;Frey RA;Stenkamp DL
小眼症（眼睛尺寸减小），通常伴有视力缺陷，是人类胎儿酒精谱系障碍（FASD）的标志。在斑马鱼中，胚胎在视网膜神经发生期间暴露于乙醇也会导致小眼症。这种小眼症部分是视网膜细胞分化减少的结果，包括光感受器。在这里，我们追求2个信号通路参与FASD发病机制的其他方面：视黄酸（RA）和音刺猬（Shh）。我们评估了在视网膜神经发生期间用乙醇处理的胚胎眼中RA和Shh信号的标记物。我们还进行了救援实验，使用外源性RA和胆固醇，这增强了Shh信号的管理。使用序贯或联合治疗，RA在任何试验浓度下均不能挽救乙醇诱导的小眼症。此外，类风湿关节炎本身引起小眼球，虽然其潜在机制与乙醇不同。有趣的是，RA处理似乎以浓度依赖性方式恢复感光细胞分化。这可能是一个独立的效果或外源性RA，因为单独的乙醇处理并没有改变眼睛中的RA信号。胆固醇注射液在任何测试浓度下也不能挽救乙醇诱导的小眼症，乙醇治疗也不能改变shh或ptc-2的表达，这通常是由Shh信号调节的。总之，这些发现表明，在视网膜神经发生期间，乙醇对眼睛发育的影响可能独立于RA和Shh信号通路。这些研究表明，基于增强或RA或Shh信号的FASD干预策略可能无法预防乙醇诱导的小眼症。
Microphthalmia (reduced eye size), generally accompanied by vision defects, is a hallmark of fetal alcohol spectrum disorder (FASD) in humans. In zebrafish, embryonic ethanol exposure over the time of retinal neurogenesis also results in microphthalmia. This microphthalmia is in part the consequence of reduced retinal cell differentiation, including photoreceptors. Here we pursue 2 signaling pathways implicated in other aspects of FASD pathogenesis: retinoic acid (RA) and Sonic hedgehog (Shh). We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also perrormed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling. Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those or ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect or exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling. Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. These studies suggest that FASD intervention strategies based upon augmentation or RA or Shh signaling may not prevent ethanol-induced microphthalmia.
登录
查看更多内容
影响因子：
9.2
作者：
EKKER, SC;UNGAR, AR;BEACHY, PA
通讯作者：
BEACHY, PA
影响因子：
2.7
作者：
Blader, P;Strähle, U
通讯作者：
Strähle, U
DOI：
10.1097/01.alc.0000125343.01149.4d
发表时间：
2004-05-01
影响因子：
3.2
作者：
Aguilera, Y;Ruiz-Gutiérrez, V;Dorado, ME
通讯作者：
Dorado, ME
影响因子：
2.5
作者：
Dlugos, Cynthia A.;Rabin, Richard A.
通讯作者：
Rabin, Richard A.
影响因子：
1.6
作者：
Hug, TE;Fitzgerald, KM;Cibis, GW
通讯作者：
Cibis, GW