Department of Biomedical Sciences and Disease, The New England College of Optometry, Boston, MA, USA.
Ophthalmic Physiol Opt. 2013 May;33(3):245-56. doi: 10.1111/opo.12054.
In chicks, ocular growth inhibition is associated with choroidal thickening and growth stimulation with choroidal thinning, suggesting a mechanistic link between the two responses. Because muscarinic antagonists inhibit the development of myopia in animal models by a non-accommodative mechanism, we tested the hypothesis that agonists would stimulate eye growth and thin the choroid. We also hypothesized that the effective growth-inhibiting antagonists would thicken the choroid.
Chicks, age 12-16 days, were used. In vivo: Agonists: Single intravitreal injections (20 μL) of oxotremorine (oxo), pilocarpine (pilo), carbachol (carb), or arecaidine (arec) were given to otherwise untreated eyes. A-scan ultrasonography was done prior to injections, and at 3, 24, 48 and 72 h. Antagonists: -10D lenses were worn on one eye for 4 days. Atropine (atro), pirenzepine (pirz), oxyphenonium (oxy) or dicyclomine (dicy) were injected (20 μL) daily into lens-wearing eyes; saline injections were done as controls. Ultrasonography was done on d1 and on d4; on d4 measurements were done before and 3 h after injections. In vitro: Paired eyecups of retinal pigment epithelium (RPE), choroid and sclera were made from 1-week old chicks. All drugs except atropine were tested on one eyecup, its pair in plain medium. Choroidal thickness was measured at various times over 48 h.
Agonists: In vivo, oxotremorine caused an increase in the rate of axial elongation (drug vs saline: 24-72 h: 338 μm vs 250 μm; p < 0.001). All except pilocarpine caused choroidal thinning by 24 h (oxo, carb and arec vs saline: -25, -35 and -46 μm vs 3 μm). In vitro, all agonists thinned choroids by 24 h (oxo: -6 vs 111 μm; pilo: 45 vs 212 μm; carb: -58 vs 65 μm; arec: 47 vs 139 μm; p < 0.05). Antagonists: Atropine, pirenzepine and oxyphenonium inhibited the development of myopia in negative lens-wearing eyes, and also caused choroidal thickening (drug vs saline: 42, 80, 88 vs 10 μm per 3 h). In vitro, pirenzepine thickened choroids by 3 h (77 vs 2 μm, p < 0.01).
Muscarinic agonists caused choroidal thinning in intact eyes and eyecups, supporting a role for acetylcholine in the choroidal response to hyperopic defocus or form deprivation. Only oxotremorine stimulated eye growth, which is inconsistent with a muscarinic receptor mechanism for antagonist-induced eye growth inhibition. The dissociation between choroidal thinning and ocular growth stimulation for the other agonists in vivo suggest separate pathways for the two.
在小鸡中，眼轴生长抑制与脉络膜增厚有关，而脉络膜刺激与变薄有关，这表明这两种反应之间存在机制联系。由于毒蕈碱拮抗剂通过非调节机制抑制动物模型近视的发展，我们假设激动剂会刺激眼生长并使脉络膜变薄。我们还假设有效的生长抑制拮抗剂会使脉络膜变厚。
使用 12-16 天大的小鸡。体内：激动剂：将氧托品（oxo）、毛果芸香碱（pilo）、卡巴胆碱（carb）或槟榔碱（arec）的单次玻璃体内注射（20 μL）给予未经其他处理的眼睛。在注射前和 3、24、48 和 72 小时进行 A 扫描超声检查。拮抗剂：-10D 透镜在一只眼睛上佩戴 4 天。阿托品类（atro）、哌仑西平（pirz）、氧苯那林（oxy）或双环胺（dicy）每天（20 μL）注射到戴镜眼；生理盐水注射作为对照。在 d1 和 d4 进行超声检查；在 d4 测量前和注射后 3 小时进行测量。体外：从 1 周大的小鸡中制作视网膜色素上皮（RPE）、脉络膜和巩膜的成对眼杯。除阿托品外，所有药物都在一个眼杯上进行了测试，其配对眼杯在普通培养基中。在 48 小时内的不同时间测量脉络膜厚度。
激动剂：体内，氧托品引起眼轴伸长率增加（药物与生理盐水：24-72 小时：338 μm 与 250 μm；p <0.001）。除毛果芸香碱外，所有药物在 24 小时内均引起脉络膜变薄（氧托品、卡巴胆碱和槟榔碱与生理盐水：-25、-35 和-46 μm 与 3 μm）。体外，所有激动剂均在 24 小时内使脉络膜变薄（氧托品：-6 与 111 μm；毛果芸香碱：45 与 212 μm；卡巴胆碱：-58 与 65 μm；槟榔碱：47 与 139 μm；p <0.05）。拮抗剂：阿托品、哌仑西平和氧苯那林抑制负透镜佩戴眼睛的近视发展，也引起脉络膜增厚（药物与生理盐水：每 3 小时 42、80、88 与 10 μm）。体外，哌仑西平在 3 小时内使脉络膜变厚（77 与 2 μm，p <0.01）。
毒蕈碱激动剂在完整的眼睛和眼杯中引起脉络膜变薄，支持乙酰胆碱在脉络膜对远视离焦或形觉剥夺的反应中发挥作用。只有氧托品刺激眼生长，这与拮抗剂诱导眼生长抑制的毒蕈碱受体机制不一致。体内其他激动剂在脉络膜变薄和眼生长刺激之间的分离表明这两种途径是分开的。
