Topical review: Potential mechanisms of atropine for myopia control

SIGNIFICANCE: Atropine is effective at slowing myopia progression in children, but the mechanism of action by which it controls myopia remains unclear. This article is an evidenced-based review of potential receptor-based mechanisms by which atropine may act to slow the progression of myopia. The rising number of individuals with myopia worldwide and the association between myopia and vision-threatening ocular pathologies have made myopia control treatments one of the fastest growing areas of ophthalmic research. High-concentration atropine (1%) is the most effective treatment for slowing myopia progression to date; low concentrations of atropine (≤0.05%) appear partially effective and are currently being used to slow myopia progression in children. While significant progress has been made in the past few decades in understanding fundamental mechanisms by which atropine may control myopia, the precise characterization of how atropine works for myopia control remains incomplete. It is plausible that atropine slows myopia via its affinity to muscarinic receptors and influence on accommodation, but animal studies suggest that this is likely not the case. Other studies have shown that, in addition to muscarinic receptors, atropine can also bind, or affect the action of, dopamine, alpha-2-adrenergic, gamma-aminobutyric acid, and cytokine receptors in slowing myopia progression. This review summarizes atropine’s effects on different receptor pathways of ocular tissues and discusses how these effects may or may not contribute to slowing myopia progression. Given the relatively broad array of receptor-based mechanisms implicated in atropine control of myopia, a single mode of action of atropine is unlikely; rather atropine may be exerting its myopia control effects directly or indirectly via several mechanisms at multiple levels of ocular tissues, all of which likely trigger the response in the same direction to inhibit eye growth and myopia progression.