Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick

Abstract

Atropine has previously been found to suppress visually induced myopia both in animals and humans. The mechanism of its action is unclear. We have studied its retinal effects in an in vitro preparation, using the retina-pigment epithelium-choroid complex of the chick eye. In vivo, deprivation myopia was induced by translucent goggles. Atropine solution was injected into the vitreous at two-day intervals. Dopamine release from the retina following atropine injection in vivo and from the in vitro retina preparation was quantified by HPLC-EC. In vitro preparations of the isolated chick retina-pigment epithelium-choroid were superfused with atropine. Light-induced potentials (local ERG), slow standing potentials from the retinal pigment epithelium/neural retina, and extracellular potassium concentrations were recorded. In line with previous findings, intravitreal injections of atropine (25 microg, 250 microg) reduced deprivation myopia in a dose-dependent manner. Atropine increased the release of the neurotransmitter dopamine into the superfusate in vitro at 100-500 microM and into the vitreous in vivo at 250 microg. Before an increase was measured in the vitreous, the retinal dopamine content was elevated. In concentrations equivalent to the intravitreal concentration to suppress myopia in vivo (200-800 microM), atropine induced spreading depression (SD) in the in vitro preparation. In contrast, muscarinic agonists, acetylcholine and pilocarpine, did not induce SD. Atropine reduced the ERG b- and d-wave, led to damped oscillations of RPE potentials, and reversed the ERG c-wave. Atropine suppressed myopia only at doses at which severe nonspecific side effects were observed in the retina. Atropine seems to intrude massively into the vital functions of the retina as indicated by the occurrence of SD. We conclude that atropine, by inducing SD, boosts neurotransmitter release from cellular stores, which may cancel out a presumed retinal signal that controls eye growth and through this, myopia.

High myopia is not associated with single nucleotide polymorphisms in the COL2A1 gene in the Chinese population

“…More and more research into genetic factors of myopia give rise to its importance, with improved understanding of its biological mechanism (2,(13)(14)(15)(16)(17)(18). The association study of candidate genes and loci has been evaluated and the available evidence suggests the involvement of certain genes and loci in myopia in different ethnic populations (19)(20)(21)(22)(23)(24)(25)(26).…”

The Influence of the Autonomic Nervous System on the Human Choroid

“…The growth inhibition effect of muscarinic blockers (atropine and pirenzepine) is well documented in animal studies (Lind et al, 1998;Schwahn et al, 2000;Luft et al, 2003;Diether et al, 2007;Nickla and Wallman 2010a;Arumugam and McBrien, 2012;Nickla et al, 2013a). Recent human clinical trials also indirectly support a role of the cholinergic system in the regulation of eye growth and myopia progression.…”

“…Muscarinic blockers may also stimulate the synthesis and release of dopamine from dopaminergic amacrine cells that ultimately increase choroidal thickness and cause retardation of ocular growth (Schwahn et al, 2000;Nickla et al, 2010b;Arumugam and McBrien, 2012). Although the mechanism through which dopamine prevents myopia is also unclear, the evidence suggest that dopamine may stimulate the synthesis and release of nitric oxide (NO) and this in turn influences choroidal thickness changes (Nickla et al, 2013b).…”

“…However, the exact anatomical site for a cholinergic mechanism regulating eye growth remains the subject of scientific debate. The retina, retinal pigment epithelium, choroid and sclera have all been implicated as potential sites of action of muscarinic antagonists (Fisher et al;1998;Schwahn et al, 2000;Yin et al, 2004;Barathi et al, 2013).…”

Vitamin D in Dry Eye and Myopia

“…Pharmacological effects using dopaminergic and cholinergic agents have been examined in experimental myopia (Dong et al, 2011b;Schmid & Wildsoet, 2004;Schwahn et al, 2000).…”