Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks.
Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks.
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DOI：
10.1016/j.exer.2010.08.021
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发表时间：
2010-11
影响因子：
3.4
通讯作者：
Dhillon, Balprit
中科院分区：
文献类型：
--
作者：
Nickla, Debora L.;Totonelly, Kristen;Dhillon, Balprit
多巴胺能系统与鸡和猴的眼生长调节有关。在这两种情况下，多巴胺D2激动剂抑制近视眼的发展，以响应形觉剥夺，并在小鸡中，负透镜以及。因为有越来越多的证据表明脉络膜对散焦的反应在眼生长调节中起作用，我们询问有效的激动剂是否也引起伴随生长抑制的脉络膜的短暂增厚。从8-12天龄开始，将安装在维可牢环上的负透镜戴在一只眼睛上。使用30 G针头通过上级颞侧巩膜玻璃体内注射（20 μl;剂量=10 nmole）激动剂（溶于盐水）或盐水。每天中午对眼睛进行注射，持续4天，并立即更换镜片。使用的激动剂是阿扑吗啡（非特异性; n=17）、喹吡罗（D2; n=10）、SKF-38393（D1; n=9）和盐水对照（n=22）。对于拮抗剂，使用相同的方案，但每天取出镜片2小时。在摘除晶状体前即刻，注射拮抗剂（20 μl;剂量=5 nmole）。使用的拮抗剂为甲基麦角新碱（非特异性; n=12）、螺哌隆（D2; n=20）、SCH-23390（D1 n=6）和生理盐水对照（n=27）。与生理盐水（连续透镜配戴）对照的比较来自激动剂实验。在透镜配戴开始时、注射前第4天以及3小时后再次使用高频A扫描超声测量轴向尺寸。在实验结束时，使用Hartinger折射计测量折射误差。阿扑吗啡和喹吡罗抑制对负透镜诱导的远视散焦的屈光反应（药物与盐水对照：-1.3和1.2 D vs-5.6 D;两者p<0.005）。这种作用是轴向的：两种药物都防止了眼球过度伸长（眼轴长度变化：233和205 μm vs 417 μ m;两者p<0.01）。两种药物还与3小时内脉络膜的短暂增厚相关（分别为41和32 um vs-1 um; p<0.01; p=0.059），但未加总：所有配戴镜片的眼睛中，脉络膜在4天内显著变薄。在负透镜配戴期间，每天两小时的无限制视力通常可防止近视的发展。螺哌隆和SCH-23390抑制了视力周期对晶状体诱导的屈光不正的改善作用（-2.9和-2.8 D vs 0.6 D; p<0.0001），然而，对眼轴长度和脉络膜厚度的影响均不显著。这些数据支持D1和D2受体在眼生长反应中的作用。
The dopaminergic system has been implicated in ocular growth regulation in chicks and monkeys. In both, dopamine D2 agonists inhibit the development of myopia in response to form deprivation, and in chicks, to negative lenses as well. Because there is mounting evidence that the choroidal response to defocus plays a role in ocular growth regulation, we asked whether the effective agonists also elicit transient thickening of the choroid concomitant with the growth inhibition. Negative lenses mounted on velcro rings were worn on one eye starting at age 8-12 days. Intravitreal injections (20 μl; dose=10 nmole) of the agonist (dissolved in saline) or saline, were given through the superior temporal sclera using a 30G needle. Eyes were injected daily at noon, for 4 days, and the lenses immediately replaced. Agonists used were apomorphine (non-specific; n=17), quinpirole (D2; n=10), SKF-38393 (D1; n=9), and saline controls (n=22). For the antagonists, the same protocol was used, but on each day, the lenses were removed for 2 hours. Immediately prior to lens-removal, the antagonist was injected (20 μl; dose=5 nmole). Antagonists used were methylergonovine (non-specific; n=12), spiperone (D2; n=20), SCH-23390 (D1 n=6) and saline controls (n=27). Comparisons to saline (continuous lens wear) controls were from the agonist experiment. Axial dimensions were measured using high frequency A-scan ultrasonography at the start of lens wear, and on day 4 prior to the injections, and then again 3 hours later. Refractive errors were measured using a Hartinger's refractometer at the end of the experiment. Apomorphine and quinpirole inhibited the refractive response to the hyperopic defocus induced by the negative lenses (drug vs saline controls: -1.3 and 1.2 D vs -5.6 D; p<0.005 for both). This effect was axial: both drugs prevented the excessive ocular elongation (change in axial length: 233 and 205 μm vs 417 um; p<0.01 for both). Both drugs were also associated with a transient thickening of the choroid over 3 hours (41 and 32 um vs –1 um; p<0.01; p=0.059 respectively) that did not summate: choroids thinned significantly over the 4 day period in all lens-wearing eyes. Two daily hours of unrestricted vision during negative lens wear normally prevents the development of myopia. Spiperone and SCH-23390 inhibited the ameliorating effects of periods of vision on lens-induced refractive error (-2.9 and –2.8 D vs 0.6 D; p<0.0001), however, the effects on neither axial length nor choroidal thickness were significant. These data support a role for both D1 and D2 receptors in the ocular growth responses.
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