Abstract：
Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs). During eye development, the optic vesicles and later the retina generate RA as a metabolite of vitamin A (retinol). Retinol is first converted to retinaldehyde by retinol dehydrogenase 10 (RDH10) and then to RA by all three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, and ALDH1A3). In early mouse embryos, RA diffuses to tissues throughout the optic placode, optic vesicle, and adjacent mesenchyme to stimulate folding of the optic vesicle to form the optic cup. RA later generated by the retina is needed for further morphogenesis of the optic cup and surrounding perioptic mesenchyme; loss of RA at this stage leads to microphthalmia and cornea plus eyelid defects. RA functions by binding to nuclear RARs at RA response elements (RAREs) that either activate or repress transcription of key genes. Binding of RA to RARs regulates recruitment of transcriptional coregulators such as nuclear receptor coactivator (NCOA) or nuclear receptor corepressor (NCOR), which in turn control binding of the generic coactivator p300 or the generic corepressor PRC2. No genes have been identified as direct targets of RA signaling during eye development, so future studies need to focus on identifying such genes and their RAREs. Studies designed to learn how RA normally controls eye development in vivo will provide basic knowledge valuable for determining how developmental eye defects occur and for improving strategies to treat eye defects.
摘要：
视黄酸（RA）通过控制RA受体（RAR）的转录调节活性，作为脊椎动物眼发育的必需信号。在眼睛发育过程中,视神经囊泡和后来的视网膜产生RA作为维生素A（视黄醇）的代谢产物。视黄醇首先通过视黄醇脱氢酶10（RDH10）转化为视黄醛，然后通过所有三种视黄醛脱氢酶（ALDH1A1，ALDH1A2和ALDH1A3）转化为RA。在早期小鼠胚胎中，RA扩散到整个光学placode的组织，视神经囊泡，和相邻的间充质刺激光学囊泡折叠形成视杯。视网膜后来产生的RA需要视杯和周围视神经间充质的进一步形态发生；此阶段RA的丧失会导致小眼症和角膜以及眼睑缺损。RA通过在激活或抑制关键基因转录的RA反应元件(RARE)处与核RAR结合而起作用。RA与RAR的结合调节转录共调节因子的募集，如核受体共激活因子（NCOA）或核受体共抑制因子（NCOR），进而控制通用共激活因子p300或通用共阻遏子PRC2的结合。没有基因被确定为眼睛发育过程中RA信号的直接靶标，因此，未来的研究需要专注于识别这些基因及其RARE。旨在了解RA如何在体内正常控制眼睛发育的研究将为确定发育性眼睛缺陷的发生方式和改进治疗眼睛缺陷的策略提供有价值的基本知识。
