Choroidal retinoic acid synthesis: A possible mediator between refractive error and compensatory eye growth
Choroidal retinoic acid synthesis: A possible mediator between refractive error and compensatory eye growth
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DOI：
10.1006/exer.1999.0813
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发表时间：
2000-04-01
影响因子：
3.4
通讯作者：
Wallman, J
中科院分区：
文献类型：
--
作者：
Mertz, JR;Wallman, J
过去二十年的研究表明，年轻眼睛的发育是由视力引导的。如果近视眼或远视眼是由镜片人为造成的，灵长类动物和雏鸟的眼睛会通过改变它们的伸长率来补偿，从而恢复到镜片前的视力状况。在视网膜上的视觉效果和眼睛生长的改变之间，究竟是什么样的化学信号起到了调节作用，目前还知之甚少。我们提出了五个发现，指出脉络膜维甲酸可能是这样的介质。首先，小鸡脉络膜叫声以11+/-3 pmol mg蛋白（-1）hr（-1）的速率将视黄醇转化为全反式视黄酸，而视网膜/RPE的速率为1.3+/-0.3，巩膜没有转化。其次，那些导致眼伸长率增加的视觉条件（扩散或负晶状体磨损）会导致全反式维甲酸合成急剧下降，几乎无法用我们的检测方法检测到。相反，导致眼伸长率下降的视觉条件（从扩散器或正晶状体磨损中恢复）产生全反式维甲酸形成的四到五倍增加。第三，发现脉络膜维甲酸与28- 32kd蛋白结合。第四，在培养中合成的脉络膜维甲酸的很大一部分存在于巩膜的富核部分。最后，在培养的巩膜中应用生理浓度的维甲酸，产生了蛋白多糖产生的抑制（通过测量硫酸盐掺入来评估），EC50为8 x 10(-7) m。维甲酸可通过影响眼伸长的视觉操作来调节，维甲酸到达巩膜的浓度足以调节巩膜蛋白多糖的形成。(C) 2000年学术出版社。
Research over the past two decades has shown that the growth of young eyes is guided by vision. If near- or far-sightedness is artificially imposed by spectacle lenses, eyes of primates and chicks compensate by changing their rate of elongation, thereby growing back to the pre-lens optical condition. Little is known about what chemical signals might mediate between visual effects on the retina and alterations of eye growth. We present five findings that point to choroidal retinoic acid possibly being such a mediator.First, the chick choroid call convert retinol into all-trans-retinoic acid at the rate of 11+/-3 pmoles mg protein(-1) hr(-1), compared to 1.3+/-0.3 for retina/RPE and no conversion for sclera. Second, those visual conditions that cause increased rates of ocular elongation (diffusers or negative lens wear) produce a sharp decrease in all-trans-retinoic acid synthesis to levels barely detectable with our assay. In contrast, visual conditions which result in decreased rates of ocular elongation (recovery from diffusers or positive lens wear) produce a four- to five-fold increase in the formation of all-trans-retinoic acid. Third, the choroidal retinoic acid is found bound to a 28-32 kD protein. Fourth, a large fraction of the choroidal retinoic acid synthesized in culture is found in a nucleus-enriched fraction of sclera. Finally, application of retinoic acid to cultured sclera at physiological concentrations produced an inhibition of proteoglycan production (as assessed by measuring sulfate incorporation) with a EC50 of 8 x 10(-7) M. These results show that the synthesis of choroidal. retinoic acid is modulated by those visual manipulations that influence ocular elongation and that this retinoic acid may reach the sclera in concentrations adequate to modulate scleral proteoglycan formation. (C) 2000 Academic Press.