TY - JOUR
T1 - Effectiveness and safety of topical levodopa in a chick model of myopia
AU - Thomson, Kate
AU - Karouta, Cindy
AU - Morgan, Ian
AU - Kelly, Tamsin
AU - Ashby, Regan
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076109559&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-54789-5
DO - 10.1038/s41598-019-54789-5
M3 - Article
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18345
ER -