Purchase this article with an account.
I.G. Morgan, P. van Rijswijk, P. Megaw; M4 Muscarinic Acetylcholine Receptors Mediate Muscarinic Block of Axial Elongation in the Chicken . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3342.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Muscarinic cholinergic antagonists inhibit axial elongation and the development of myopia in vivo and sulphate incorporation into scleral glycosaminoglycans in vitro in chickens. We have investigated the effects of the muscarinic antagonists atropine, pirenzepine and MT3 on these measures. Methods:Form–deprived chicks received daily intravitreal injections of the antagonists for 9 days. On the 10th day, axial length (AL) was measured by A–scan ultrasonography. For in vitro studies, scleral buttons were incubated with 35S–sulphate in the presence of the antagonists, and sulphate incorporation into scleral glycosaminoglycans was measured. Results:Form–deprivation led to a marked increase in AL which intravitreal injections of atropine, pirenzepine and MT3 suppressed in a dose–dependent manner. The estimated vitreal dose for 50% suppression was 0.106mM for atropine and 1.178mM for pirenzepine. MT3 was also effective. In vitro sulphate incorporation into glycosaminoglycans was not inhibited by even high doses of pirenzipine (10mM) in scleral buttons derived from control and form–deprived sclera, or MT3 (250pM, 25nM and 250nM). In comparison, atropine inhibited sulphate incorporation into scleral glycosaminoglycans by 50% at 30µM. Conclusions: Relative to atropine, ∼10–fold higher doses of pirenzepine were required to prevent axial elongation, suggesting a role for M1 or M4 muscarinic receptor subtypes. The ability of MT3 to prevent axial elongation supports the involvement of the M4 subtype, rather than the M1 subtype. The ineffectiveness of pirenzepine and MT3 on sulphate incorporation into scleral glycosaminglycans in vitro suggests that a different form of receptor mediates this effect. The different pharmacological profiles of the two effects suggest that direct effects of the muscarinic antagonists on scleral glycosaminoglycan synthesis are not responsible for the inhibition of axial elongation in vivo, although they do not exclude an effect of the antagonists on the sclera affecting axial elongation via an as yet undescribed mechanism. We appreciate the financial support of Regenera in the presentation of this work.
This PDF is available to Subscribers Only