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

Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.