Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME.

Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME.
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DOI:
10.1016/j.exer.2009.01.012
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发表时间:
2009-06
影响因子:
3.4
通讯作者:
Lytle, Grace
Lytle, Grace
中科院分区:
医学3区
文献类型:
--
作者:
Nickla, Debora L.;Damyanova, Petya;Lytle, Grace

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在鸟类中,脉络膜在眼睛生长的视觉调节中起作用,响应于近视散焦而变厚,并且响应于远视散焦而变薄,在这两种情况下将视网膜朝向图像平面移动。这种反应是迅速的,在散焦刺激的几个小时内发生。这些变化始终与巩膜的较慢变化相关,这导致轴向伸长的适当变化,响应于近视散焦而减少生长,响应于远视散焦而增加生长。巩膜反应的分子机制涉及细胞外基质分子合成的变化,然而,导致脉络膜厚度变化的分子机制尚不清楚。然而,有证据表明,它可能涉及气体信号分子一氧化氮,因为一氧化氮是一种有效的平滑肌松弛剂,注射非特异性一氧化氮合酶抑制剂L-NAME短暂抑制增厚反应。有趣的是,它还根据两种反应之间的机械联系解除了对眼部生长的抑制。如果一氧化氮是眼睛生长的视觉调节信号级联的一部分,那么确定分子的来源就很重要。作为这样做的第一步,我们使用了各种更具体的NOS抑制剂,并研究了它们对脉络膜和生长反应的影响。鸡(7-12日龄)的一只眼睛上安装+10 D镜片。当天,使用以下抑制剂的单次玻璃体内注射(30 μl):nNOS抑制剂N ω-丙基-L-精氨酸(n=12)、iNOS抑制剂L-NIL(n=16)、eNOS/iNOS抑制剂L-NIO(n=15)、非特异性抑制剂L-NMMA(n=30)或生理盐水(n=18)。在实验开始时以及实验后7、24和48小时,使用高频A扫描超声测量眼睛尺寸。我们发现,nNOS抑制剂N ω-丙基-L-精氨酸对脉络膜反应有相同的抑制作用,并解除生长反应的抑制,L-NAME也是如此;除L-NMMA外,其他抑制剂都没有任何作用。我们的结论是,脉络膜代偿反应的影响,可能从内在的脉络膜神经元,或副交感神经支配的睫状神经节和/或翼腭神经节的nNOS。
In birds, the choroid plays a role in the visual regulation of eye growth, thickening in response to myopic defocus, and thinning in response to hyperopic defocus, in both cases moving the retina towards the image plane. This response is rapid, occurring within hours of the defocus stimulus. These changes are consistently associated with slower changes in the sclera, that result in the appropriate changes in axial elongation, decreasing growth in response to myopic defocus and increasing it in response to hyperopic defocus. The molecular mechanisms underlying the scleral response involve changes in the synthesis of extracellular matrix molecules, however, those underlying the changes in choroidal thickness are not known. However, evidence suggests that it may involve the gaseous signal molecule nitric oxide, as nitric oxide is a potent smooth muscle relaxant, and injections of the non-specific nitric oxide synthase inhibitor L-NAME transiently inhibits the thickening response. Interestingly, it also dis-inhibits ocular growth, in accordance with a mechanistic link between the two responses. If nitric oxide is part of the signal cascade underlying the visual regulation of eye growth, it would be important to ascertain the source of the molecule. As a first step towards doing so, we used various more specific NOS inhibitors and studied their effects on the choroidal and growth responses. Birds (7–12 days old) were fitted with +10 D lenses on one eye. On that day, single intravitreal injections (30 μl) of the following inhibitors were used: nNOS inhibitor N ω-propyl-L-arginine (n=12), iNOS inhibitor L-NIL (n=16), eNOS/iNOS inhibitor L-NIO (n=15), non-specific inhibitor L-NMMA (n=30) or physiological saline (n=18). Ocular dimensions were measured using high-frequency A-scan ultrasonography at the start of the experiment, and at 7, 24 and 48 hours after. We found that the nNOS inhibitor N ω-propyl-L-arginine had the same inhibitory effects on the choroidal response, and dis-inhibition of the growth response, as did L-NAME; neither of the other inhibitors had any effect except L-NMMA. We conclude that the choroidal compensatory response is influenced by nNOS, possibly from the intrinsic choroidal neurons, or the parasympathetic innervation from the ciliary and/or pterygopalatine ganglia.
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