Nitric oxide synthase inhibitors prevent the growth-inhibiting effects of quinpirole.
Nitric oxide synthase inhibitors prevent the growth-inhibiting effects of quinpirole.
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DOI：
10.1097/opx.0000000000000041
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发表时间：
2013-11
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影响因子：
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通讯作者：
Totonelly K
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作者：
Nickla DL;Lee L;Totonelly K
多巴胺和一氧化氮（NO）都参与了介导眼生长抑制的信号级联反应。如果两者都是同一条路径的一部分，那么哪一个在另一个之前？我们测试的假设，多巴胺的行为上游的NO，通过使用两种NOS抑制剂与多巴胺激动剂quinpirole组合，并测量对眼生长率的影响。小鸡从13日龄开始佩戴-10 D镜片或扩散器（FD）4天。实验眼每天接受以下20 μ l注射：喹吡罗：透镜：n = 12; FD：n = 20; n-ω-丙基-L-精氨酸（n-PLA）：透镜：n = 6; FD：n = 4;喹吡罗+n-PLA：透镜：n = 17; FD：n = 19;喹吡罗+L-NIO：透镜：n = 12; FD：n = 12。盐水注射作为对照。在开始时、第5天、注射前和注射后3小时进行高频超声检查。在第5天测量屈光度。正如预期的那样，喹吡罗在两种范例中都防止了轴性近视的发展。然而，当喹吡罗与任一NOS抑制剂联合使用时，与喹吡罗相比，眼睛变得近视（FD：n-PLA：− 5.9D vs − 3.4D; L-NIO：− 5.8D vs − 3.4D; LENS：n-PLA：− 3.5D vs − 0.4D;所有p <0.05; L-NIO不显著）。这是与喹吡罗相比玻璃体腔生长解除抑制的结果（FD：n-PLA：401 vs 275 μ m/4d; L-NIO：440 vs 275 μ m/4d; LENS：n-PLA：407 vs 253/4d; L-NIO：403 vs 253 μ m/4d; p <0.05）。只有n-PLA防止了佩戴镜片的眼睛中喹吡罗诱导的脉络膜增厚（0 vs 31 μ m/3hr; p <0.05）。在FD眼中，任一药物均不能抑制脉络膜增厚。多巴胺在形觉剥夺和负透镜配戴中的NO和脉络膜反应的上游起作用，在介导眼生长抑制的信号级联中起作用。NOS抑制剂都不能抑制FD眼中的脉络膜增厚，这表明两种范式中的脉络膜机制不同。
Both dopamine and nitric oxide (NO) have been implicated in the signal cascade mediating ocular growth inhibition. If both are part of the same pathway, which precedes the other? We tested the hypothesis that dopamine acts upstream of NO, by using two NOS inhibitors in combination with the dopamine agonist quinpirole, and measuring the effects on ocular growth rate. Chicks wore −10 D lenses or diffusers (FD) for 4d starting at age 13d. Experimental eyes received daily 20 μl injections of the following: Quinpirole: lens: n=12; FD: n=20; n-ω-propyl-L-arginine (n-PLA): lens: n=6; FD: n=4; quinpirole + n-PLA: lens: n=17; FD: n=19; quinpirole + L-NIO: lens: n=12; FD: n=12. Saline injections were done as controls. High frequency ultrasonography was done at the start, and on day 5, prior to injections and 3 hours later. Refractions were measured on day5. As expected, quinpirole prevented the development of axial myopia in both paradigms. When quinpirole was combined with either NOS inhibitor, however, eyes became myopic compared to quinpirole (FD: n-PLA: −5.9D vs −3.4D; L-NIO: −5.8D vs −3.4D; LENS: n-PLA: −3.5D vs −0.4D; p<0.05 for all; L-NIO was not significant). This was the result of a dis-inhibition of vitreous chamber growth vs quinpirole (FD: n-PLA: 401 vs 275 μm/4d; L-NIO: 440 vs 275 μm/4d; LENS: n-PLA: 407 vs 253/4d; L-NIO: 403 vs 253 μm/4d; p<0.05). Only n-PLA prevented the quinpirole-induced choroidal thickening in lens-wearing eyes (0 vs 31 μm/3hr; p<0.05). Choroidal thickening was not inhibited by either drug in FD eyes. Dopamine acts upstream of NO and the choroidal response in the signal cascade mediating ocular growth inhibition in both form deprivation and negative lens wear. That neither NOS inhibitor inhibits choroidal thickening in FD eyes suggests that the choroidal mechanisms differ in the two paradigms.