Methylphenidate Inhibits the Development of Myopia by Altering Dopamine and Norepinephrine Reuptake

Dopaminergic dysregulation plays a critical role in myopia development in animal models. Although its relevance to human myopia remains uncertain, the observation that methylphenidate hydrochloride (MPH)-a dopamine (DA) and norepinephrine (NE) uptake inhibitor-slows myopia progression in children suggests a possible link. This study aimed to investigate whether MPH can inhibit myopic growth and elucidate the underlying mechanisms using an animal model.

MPH was administered via oral, topical, or intravitreal routes for 7 days (minimum 5 per group) to chicks undergoing form-deprivation myopia (FDM). Myopia was assessed by refraction and axial length. Retinal DA and NE dynamics-including synthesis, release, uptake, breakdown (DA only), extracellular levels, and receptor sensitivity-were evaluated using mass spectrometry and chronoamperometry (minimum 5 per group). DA and NE receptors were pharmacologically blocked (DA = spiperone, SCH-23390; and NE = yohimbine) to determine their role in MPH's anti-myopic effects.

MPH inhibited FDM via all administration routes (oral = 55%, P < 0.05, topical = 45%, P < 0.05, and intravitreal = 87%, P < 0.05 protection against myopic growth). It enhanced DA and NE synthesis while blocking their uptake, resulting in elevated extracellular levels. MPH's anti-myopic effects were abolished when DA or NE receptors were pharmacologically blocked. Additionally, NE receptor stimulation alone inhibited FDM (P < 0.05).

MPH suppresses experimental myopia, with its effects linked to increased extracellular levels of DA and NE. These findings align with the anti-myopic effects observed in clinical studies, supporting a role for DA in human myopia and suggesting that NE may also contribute to the regulation of ocular growth.