Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning.

Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning.
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DOI:
10.1111/opo.12054
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发表时间:
2013-05
期刊:
Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)
影响因子:
--
通讯作者:
Wallman J
Wallman J
中科院分区:
其他
文献类型:
--
作者:
Nickla DL;Zhu X;Wallman J

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在雏鸡中,眼生长抑制与脉络膜增厚和生长刺激与脉络膜变薄相关,表明两种反应之间存在机械联系。由于毒蕈碱拮抗剂在动物模型中通过非抑制机制抑制近视的发展,我们测试了激动剂刺激眼睛生长和脉络膜变薄的假设。我们还假设,有效的生长抑制拮抗剂将抑制脉络膜。使用12-16日龄的雏鸡。体内:激动剂:单次玻璃体内注射(20 μL)氧震颤素(oxo)、毛果芸香碱(pilo)、卡巴胆碱(carb)或槟榔碱(arecaidine)至其他未治疗的眼睛。在注射前以及注射后3、24、48和72 h进行A扫描超声检查。拮抗剂:将10 D镜片戴在一只眼睛上4天。每天向佩戴镜片的眼内注射阿托品(atro)、哌仑西平(pirz)、氧苯铵(oxy)或双环胺(dicyclomine)(20 µL);注射生理盐水作为对照。在第1天和第4天进行超声检查;在第4天,在注射前和注射后3小时进行测量。从1周龄雏鸡制备视网膜色素上皮(RPE)、脉络膜和巩膜的成对眼杯。除阿托品外,所有药物均在一个眼杯上进行测试,其对在普通培养基中。在48 h内的不同时间测量脉络膜厚度。激动剂:在体内,氧化震颤素导致轴向伸长速率增加(药物vs生理盐水:24-72 h:338 µm vs 250 µ m; p < 0.001)。除毛果芸香碱外,所有药物均在24小时内导致脉络膜变薄(氧代、碳水化合物和阿雷克vs生理盐水:−25、−35和−46 µm vs 3 µm)。在体外,所有激动剂在24小时内使脉络膜变薄(氧:-6 vs 111 µm; pilo:45 vs 212 µm;碳水化合物:-58 vs 65 µm; arec:47 vs 139 µm; p < 0.05)。拮抗剂:阿托品、哌仑西平和羟苯铵可抑制负镜片配戴眼的近视发展,也可引起脉络膜增厚(药物vs生理盐水:42、80、88 vs 10 µm/3 h)。在体外,哌仑西平使脉络膜增厚3 h(77 vs 2 µm,p < 0.01)。毒蕈碱激动剂引起脉络膜变薄在完整的眼睛和eyecups,支持的作用,乙酰胆碱在脉络膜反应远视散焦或形觉剥夺。只有oxotremorine刺激眼睛的生长,这是不一致的毒蕈碱受体拮抗剂诱导的眼睛生长抑制机制。其他激动剂在体内的脉络膜变薄和眼生长刺激之间的分离表明两者有不同的途径。
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. 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 µrn; 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.
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