Abstract
Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the excessive ocular growth associated with the development of myopia. Here we show that intravitreal or topical application of levodopa, which is widely used in the treatment of neurological disorders involving dysregulation of the dopaminergic system, inhibits the development of experimental myopia in chickens. Levodopa slows ocular growth in a dose dependent manner in chicks with a similar potency to atropine, a common inhibitor of ocular growth in humans. Topical levodopa remains effective over chronic treatment periods, with its effectiveness enhanced by coadministration with carbidopa to prevent its premature metabolism. No changes in normal ocular development (biometry and refraction), retinal health (histology), or intraocular pressure were observed in response to chronic treatment (4 weeks). With a focus on possible clinical use in humans, translation of these avian safety findings to a mammalian model (mouse) illustrate that chronic levodopa treatment (9 months) does not induce any observable changes in visual function (electroretinogram recordings), ocular development, and retinal health, suggesting that levodopa may have potential as a therapeutic intervention for human myopia.
Highlights
Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the excessive ocular growth associated with the development of myopia
Correction of the refractive error does not prevent the development of these conditions, the chances of which increase with the severity of myopia, as it does not address the excessive elongation of the eye[4]
In multiple species, retinal dopamine synthesis and release has been shown to be significantly down-regulated during the development of experimental myopia[9,10,11,12,13], whilst pharmacological administration of dopamine agonists, which mimic the effects of dopamine, have been shown to inhibit the development of experimental myopia
Summary
Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the excessive ocular growth associated with the development of myopia. Based on the potential role of dopamine in the regulation of ocular growth, this article investigates whether topical administration of levodopa, a drug widely used to treat neurological disorders involving dopaminergic disfunction[28], can inhibit ocular growth and prevent the development of experimental myopia in an animal model (chicken). We show that levodopa slows ocular growth and inhibits experimental myopia in a dose-dependent manner in chicks with a similar potency to atropine, whilst not affecting ocular health across those parameters tested following chronic administration For translational potential, this avian safety data was further complemented in a second, mammalian, model by analysing the effects of chronic levodopa treatment on ocular safety in mice
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