Retinoid effects in purified cultures of chick embryo retina neurons and photoreceptors.

Retinoid effects in purified cultures of chick embryo retina neurons and photoreceptors.
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发表时间:
1993-07
影响因子:
4.4
通讯作者:
D. L. Stenkamp;J. K. Gregory;R. Adler
D. L. Stenkamp;J. K. Gregory;R. Adler
中科院分区:
医学2区
文献类型:
--
作者:
D. L. Stenkamp;J. K. Gregory;R. Adler

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目的研究视黄酸、视黄醇和11-顺式视黄醛对培养的鸡胚视网膜神经细胞增殖、分化和存活的影响,描述培养细胞对这些维甲酸的代谢转化。方法在无神经胶质细胞低密度培养的视网膜神经细胞中加入维甲酸,观察在不同条件下分化并存活的神经元和光感受器的数量。提取细胞和条件培养液,用高压液相色谱鉴定和定量维甲酸代谢产物。结果维甲酸处理6d后,分化的光感受器数量呈剂量依赖性增加,非光感受器神经元的增加也较少。在培养开始时添加维甲酸比在培养后期添加更有效,但它们并不刺激细胞增殖。药效顺序为视黄醇&11-顺式视黄醛&视黄酸。外源维甲酸在24小时孵育期后原封不动地恢复;视黄醇也是稳定的和未代谢的,除了形成少量的视黄酸乙酯。11-顺式视黄醛稳定性较差,可同时代谢成维甲酸和视黄醇。结论视黄醇、11-顺式视黄醛和视黄酸可促进培养的胚胎视网膜神经元和光感受器在无神经胶质细胞和视网膜色素上皮的情况下存活(或可能分化)。虽然维甲酸可能通过与这种维甲酸的已知核受体之一相互作用来发挥作用,但视黄醇在没有代谢转化为维甲酸的情况下的有效性表明,可能存在一种独特的、尚未发现的受体。
PURPOSE To investigate the effects of retinoic acid, retinol, and 11-cis retinaldehyde on proliferation, differentiation, and survival of cultured embryonic chick neural retina cells; to describe the metabolic transformations of these retinoids by the cultured cells. METHODS Retinoids were added to glia-free, low-density cultures of neural retina cells, which underwent subsequent examination to determine the numbers of neurons and photoreceptors that differentiated and survived under differing conditions. Cells and conditioned medium were extracted to identify and quantify retinoid metabolic products by high pressure liquid chromatography. RESULTS Retinoid treatment resulted in dose-dependent increases in the number of differentiated photoreceptors present in the cultures after 6 days; smaller increases in nonphotoreceptor neurons were also observed. Retinoids were more effective when added at culture onset than at later times, but they did not stimulate cell proliferation. The order of potency was retinol > 11-cis retinaldehyde > retinoic acid. Exogenous retinoic acid was recovered unmodified after a 24-hr incubation period; retinol was also stable and unmetabolized, except for the formation of a small quantity of retinyl acetate. 11-cis retinaldehyde was less stable, and was metabolized into both retinoic acid and retinol. CONCLUSIONS Retinol, 11-cis retinaldehyde, and retinoic acid can promote the survival (and possibly differentiation) of cultured embryonic retina neurons and photoreceptors in the absence of glia and retinal pigment epithelium. Although retinoic acid is likely to function by interacting with one of the known nuclear receptors for this retinoid, the effectiveness of retinol in the absence of metabolic transformation into retinoic acid suggests the possible existence of a distinct, yet undiscovered receptor.