Kelley M W, Turner J K, Reh T A
Department of Biological Structure, University of Washington, Seattle 98195.
Development. 1994 Aug;120(8):2091-102. doi: 10.1242/dev.120.8.2091.
The results of several recent studies have demonstrated that cell commitment and differentiation in the developing vertebrate retina are influenced by cell-cell interactions within the microenvironment. Retinoic acid has been shown to influence cell fates during development of the nervous system, and retinoic acid has been detected in the embryonic retina. To determine whether retinoic acid mediates the differentiation of specific neuronal phenotypes during retinal histogenesis, we treated dissociated cell cultures of embryonic and neonatal rat retina with varying concentrations of all-trans or 9-cis retinoic acid and analyzed the effects on cell fate using neuron and photoreceptor-specific antibodies. Addition of exogenous retinoic acid caused a dose-dependent, specific increase in the number of cells that developed as photoreceptors in culture throughout the period of retinal neurogenesis. In the same cultures, retinoic acid also caused a dose-dependent decrease in the number of cells that developed as amacrine cells. Also, results of double-labeled immunohistochemical studies using bromodeoxyuridine demonstrated that the primary effect of retinoic acid was to influence progenitor cells to develop as newly generated rod photoreceptors. Since retinoic acid and at least one of the retinoic acid receptors (RAR alpha) have been localized to the developing neural retina, these results suggest that retinoic acid may play a role in the normal development of photoreceptor cells in vivo.
最近的几项研究结果表明，在发育中的脊椎动物视网膜中，细胞的定向分化受微环境中细胞间相互作用的影响。视黄酸已被证明在神经系统发育过程中影响细胞命运，并且在胚胎视网膜中已检测到视黄酸。为了确定视黄酸是否在视网膜组织发生过程中介导特定神经元表型的分化，我们用不同浓度的全反式或9-顺式视黄酸处理胚胎和新生大鼠视网膜的解离细胞培养物，并使用神经元和光感受器特异性抗体分析对细胞命运的影响。在整个视网膜神经发生期间，添加外源性视黄酸导致培养物中发育为光感受器的细胞数量呈剂量依赖性、特异性增加。在相同的培养物中，视黄酸还导致发育为无长突细胞的细胞数量呈剂量依赖性减少。此外，使用溴脱氧尿苷进行的双标记免疫组织化学研究结果表明，视黄酸的主要作用是影响祖细胞发育为新生成的视杆光感受器。由于视黄酸和至少一种视黄酸受体（RARα）已定位到发育中的神经视网膜，这些结果表明视黄酸可能在体内光感受器细胞的正常发育中起作用。
