Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning
Version of Record online: 12 MAY 2013
Ophthalmic & Physiological Optics © 2013 The College of Optometrists
Ophthalmic and Physiological Optics
Special Issue: Understanding & Controlling Myopia - Where We Are Now. A compilation to honour the research achievements and mark the passing of Josh Wallman
Volume 33, Issue 3, pages 245–256, May 2013
How to Cite
Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning. Ophthalmic Physiol Opt 2013; 33: 245–256. doi: 10.1111/opo.12054, & .
- Issue online: 12 MAY 2013
- Version of Record online: 12 MAY 2013
- Manuscript Accepted: 6 MAR 2013
- Manuscript Received: 3 SEP 2012
- eye growth
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.