Visually induced changes in components of the retinoic acid system in fundal layers of the chick

Visually induced changes in components of the retinoic acid system in fundal layers of the chick
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DOI:
10.1006/exer.1999.0762
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发表时间:
2000-01-01
影响因子:
3.4
通讯作者:
Schaeffel, F
Schaeffel, F
中科院分区:
医学3区
文献类型:
--
作者:
Bitzer, M;Feldkaemper, M;Schaeffel, F

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眼睛的生长是通过视网膜释放的信使进行视觉调节的。视网膜涉及一种尚不为人所知的算法来分析投影的图像,以确保眼睛后部的适当生长速度。维甲酸(RA)是一种可以起到生长控制作用的生化候选物质。以前的工作(Seko,Shimokawa和Tokoro,1996;Mertz等人,1999)已经表明,视网膜和脉络膜RA的水平确实可以预测地分别受到导致近视或远视的视觉条件的影响。我们研究了参与RA合成的乙醛脱氢酶-2(AHD2)和视黄醛脱氢酶-2(RALDH2)在眼底组织中的表达,以及在什么水平上视觉对RA水平的影响可能被控制。Northern印迹分析发现,负性镜片治疗3天后,视网膜AHD2的mRNA水平上调(负性镜片将图像置于视网膜后面)。在正性镜片(正性镜片将图像放在视网膜前面)治疗6小时后,RA受体RAR-β的视网膜mRNA的丰度已经上调。上调持续了至少一周。最后,我们研究了RA合成的抑制剂双硫兰对眼睛生长的视觉控制的影响。我们发现磨砂护目镜(剥夺近视)对近视有抑制作用,但对+7D或-7D镜片引起的屈光不正没有明显的抑制作用。我们的结果与RA可能在眼睛生长的视觉控制中发挥作用的假设是一致的。RA系统与许多其他候选基因(多巴胺、胆碱能药物、阿片类药物)的不同之处在于,它区分了正性和负性离焦,类似于直接早期基因Zenk(Stell等人,1999年)。这些变化的确切时间动力学仍有待研究,因为RA的变化可能与已经发生的生长变化有关,而不是与信号级联的初始步骤有关。(C)2000年学术出版社。
Eye growth is visually regulated via messengers that are released from the retina. The retina involves a yet unknown algorithm to analyse the projected image so that the appropriate growth rates for the back of the eye are ensured. One biochemical candidate that could act as a growth controller, is retinoic acid (RA). Previous work (Seko, Shimokawa and Tokoro, 1996; Mertz et al., 1999) has shown that retinal and choroidal RA levels are indeed predictably changed by visual conditions that cause myopia or hyperopia, respectively. We have studied in which fundal tissues aldehyde dehydrogenase-2 (AHD2) and retinaldehyde dehydrogenase-2 (RALDH2), enzymes involved in RA synthesis, are expressed and at which levels the effects of vision on RA levels may be controlled. Using Northern blot analysis, we have found that the retinal mRNA level of the AHD2 is up-regulated after 3 days of treatment with negative lenses (negative lenses place the image behind the retina). The abundance of the retinal mRNA of a RA receptor, RAR-beta, was up-regulated already after 6 hr of treatment with positive lenses (positive lenses place the image in front of the retina). The up-regulation persisted for at least 1 week. Finally, we have studied the effects of an inhibitor of RA synthesis, disulfiram, on the visual control of eye growth. We found inhibition of myopia as induced by frosted goggles ('deprivation myopia') but no significant inhibitory effects on refractive errors induced by +7D or -7D lenses. Our results are in line with the hypothesis that RA may play a role in the visual control of eye growth. The RA system differs from a number of other candidates (dopamine, cholinergic agents, opiates) in that it distinguishes between positive and negative defocus, similar tea the immediate early gene ZENK (Stell et al., 1999). The exact time kinetics of the changes have still to be worked out since it is possible that the changes in RA relate to already occurring changes in growth rather than to initial steps of the signaling cascade. (C) 2000 Academic Press.