Muscarinic mechanisms in myopia and ocular growth

Abnormal ocular growth results in the common vision disorders myopia (near-sightedness) or hyperopia (far-sightedness). Ocular growth must be precisely regulated to match the combined refractive power of the lens and cornea to the distance between the lens and retina so that distant objects are focussed upon the retina with neutral accommodation. This regulation of ocular growth is a function of the clarity of images to the eye and of processing of visual information by the retina. Several subtypes of retinal amacrine cells are believed to be required to properly guide the growth of the eye and promote excessive growth during deprivation of patterned images. Myopia usually results from excessive axial elongation of the eye, can be induced by form-deprivation, and can be prevented by chronic administration of muscarinic antagonists in several species, including humans. The focus of this dissertation is to investigate the role of cholinergic amacrine cells and muscarinic receptors in visually guided ocular growth. The paradigm of form deprivation myopia (FDM) is studied commonly in chicks, and, accordingly, was used in the current work.; Three different isoforms of muscarinic acetylcholine receptor (mAChR) were localized to amacrine, bipolar and ganglion cells in the retina. These mAChRs were also detected in the retinal pigmented epithelium, choroid, and ciliary body of the chick eye. The distribution of mAChRs is consistent with a role for cholinergic pathways in visually guided ocular growth. I characterized the effects of neurotoxins upon different populations of retinal cells (cholinergic amacrine cells in particular) and upon normal and form-deprivation-induced ocular growth. I tested whether the muscarinic antagonist atropine could suppress FDM in toxin-treated eyes. The selective cholinotoxin, ethylcholine mustard aziridinium (ECMA) and a less-selective excitotoxin, quisqualic acid (QA), destroyed most (all in the case of QA) cholinergic amacrine cells, yet did not affect normal ocular growth or FDM. Furthermore, atropine retained its ability to suppress FDM in both ECMA and QA-treated eyes. In conclusion, it is unlikely that cholinergic amacrine cells and mAChRs in the retina are required for visually guided ocular growth, and that atropine suppresses FDM by acting at extraretinal sites or at non-muscarinic receptors.