Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.
Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.
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DOI：
10.1016/j.alcohol.2014.11.001
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发表时间：
2015-03
期刊：
影响因子：
2.3
通讯作者：
Marrs, James A.
中科院分区：
文献类型：
--
作者：
Muralidharan, Pooja;Sarmah, Swapnalee;Marrs, James A.
胎儿酒精谱系障碍（FASD）是由产前酒精暴露引起的，产生颅面、感觉、运动和认知缺陷。FASD在低社会经济人群中非常普遍，经常伴有营养不良。与fasd相关的眼部病变包括小眼症、视神经发育不全和白内障。本研究表征了特定的视网膜组织缺陷，确定了视网膜发育过程中的乙醇敏感阶段，并剖析了营养补充剂，如维甲酸（RA）和叶酸（FA）对乙醇诱导的视网膜缺陷的影响。暴露于病理生理浓度的乙醇（在囊胚中期通过体细胞发育过渡期间；受精后2-24小时[hpf]）改变了参与视网膜细胞分化的关键转录因子表达，并产生严重的视网膜神经节细胞、光感受器和神经胶质分化缺陷。乙醇暴露不改变视网膜细胞分化诱导，但增加视网膜细胞死亡和增殖。RA和FA营养素的共同补充挽救了视网膜感光细胞和神经节细胞分化缺陷。乙醇暴露在视网膜形态发生阶段（16-24 hpf）产生的视网膜缺陷与乙醇暴露在2-24 hpf之间所见的相似。值得注意的是，在乙醇敏感时间窗（16-24 hpf）内，RA共补充适度地挽救了这些缺陷，而FA共补充显示了视神经和光感受器分化缺陷的显著拯救。有趣的是，乙醇暴露后补充RA，而不是FA，可以逆转乙醇诱导的视神经和光感受器分化缺陷。我们的研究结果表明，各种乙醇敏感事件是fasd相关视网膜缺陷的基础。类维生素a和叶酸等营养补充剂可有效缓解乙醇诱导的视网膜缺陷。
Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.
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DOI：
10.1111/j.1530-0277.2011.01511.x
发表时间：
2011-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Kashyap B;Frey RA;Stenkamp DL
通讯作者：
Stenkamp DL
影响因子：
1.6
作者：
Hug, TE;Fitzgerald, KM;Cibis, GW
通讯作者：
Cibis, GW
影响因子：
2.3
作者：
GUERRI, C;SANCHIS, R
通讯作者：
SANCHIS, R
DOI：
10.1242/dev.104380
发表时间：
2014-07
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Laranjeiro R;Whitmore D
通讯作者：
Whitmore D
影响因子：
3.7
作者：
Ali S;van Mil HG;Richardson MK
通讯作者：
Richardson MK