Ophthalmic Research Institute, Section of Neurobiology of the Eye, University of Tuebingen, Tuebingen, Germany.
Institute for Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Ophthalmic Res. 2021;64(4):664-674. doi: 10.1159/000515755. Epub 2021 Mar 30.
Atropine, a muscarinic antagonist, is known since the 19th century to inhibit myopia development in children. One of its effects is that it stimulates choroidal thickening. Thicker choroids, in turn, have been linked to myopia inhibition. We used the atropine-stimulated choroidal response in the chicken to learn more about the time courses and amplitudes of the effects of atropine, as well as whether repeated applications lead to accumulation or desensitization.
Intravitreal injections containing 250 µg atropine sulfate were performed in 1 eye around 10:00 in the morning, the fellow eye received vehicle. Chickens with bilateral vehicle injections served as controls. Choroidal thickness was measured over the day for every 2-3 h in alert animals, using spectral domain optical coherence tomography, with 3-5 independent measurements in each eye. Three experiments were done - (1) single injection and time course measured over 1 day, (2) single injection and time course measured over 4 days, and (3) daily injections and time course measured over 4 days for measuring the effects of atropine on vitreal, retinal, and choroidal dopamine, and 3,4-dihydroxyphenylacetic acid levels by using high-performance liquid chromatography with electrochemical detection.
Atropine induced an increase in choroidal thickness by about 60 percent, with a peak amplitude after about 2 h. The effect persisted only for a few hours and had nearly disappeared by evening. Initially, similar amounts of choroidal thickening were observed in vehicle-injected fellow eyes but recovery to baseline was faster. When atropine was injected daily for 4 days, choroids thickened every day with similar amplitudes and time courses, with no signs of either accumulation or desensitization effects. Interestingly, while dopamine release from the retina was stimulated by atropine and followed approximately, the time course of choroidal thickening, its tissue concentration dropped in the choroid.
Even at relatively high intravitreal doses, effects of atropine on choroidal thickness remained transient, similar to its effects on retinal dopamine. With repeated application every day, the diurnal patterns of choroidal thickening could be reproduced for 4 days with similar amplitudes and time courses. The transient nature of the effects of atropine on the choroid may be relevant for application protocols of atropine against myopia.
阿托品是一种毒蕈碱拮抗剂，自 19 世纪以来就已被证实可抑制儿童近视发展。其作用之一是刺激脉络膜增厚。脉络膜增厚反过来又与近视抑制有关。我们使用鸡的阿托品刺激脉络膜反应来进一步了解阿托品作用的时间过程和幅度，以及重复应用是否会导致积累或脱敏。
在上午 10 点左右，每只眼的玻璃体内注射 250µg 硫酸阿托品，对侧眼注射载体。双眼注射载体的鸡作为对照。使用谱域光学相干断层扫描（OCT）在警觉动物中每 2-3 小时测量一天中的脉络膜厚度，每只眼进行 3-5 次独立测量。进行了三项实验——（1）单次注射和 1 天的时间过程测量，（2）单次注射和 4 天的时间过程测量，以及（3）每天注射和 4 天的时间过程测量，以通过高效液相色谱电化学检测测量阿托品对玻璃体、视网膜和脉络膜多巴胺和 3,4-二羟基苯乙酸水平的影响。
阿托品引起脉络膜厚度增加约 60%，约 2 小时后达到峰值幅度。该作用仅持续几个小时，到傍晚时几乎消失。最初，在注射载体的对侧眼也观察到相似程度的脉络膜增厚，但恢复到基线较快。当阿托品每天注射 4 天，脉络膜每天都增厚，幅度和时间过程相似，没有积累或脱敏作用的迹象。有趣的是，虽然阿托品刺激视网膜多巴胺释放并大致遵循其时间过程，但脉络膜中的多巴胺组织浓度下降。
即使在相对较高的玻璃体内剂量下，阿托品对脉络膜厚度的作用仍然是短暂的，与它对视网膜多巴胺的作用相似。每天重复应用时，脉络膜增厚的昼夜模式可在 4 天内以相似的幅度和时间过程重现。阿托品对脉络膜作用的短暂性可能与阿托品治疗近视的应用方案有关。
