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Kate Thomson, Cindy Karouta, Regan Scott Ashby; Atropine’s inhibition of experimental myopia in chickens can be disrupted by serotonergic stimulation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3397.
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Atropine is classified as a muscarinic-cholinergic (mAChR) antagonist. However, it is unclear if this is the receptor family by which it exerts its anti-myopia effects. In addition to mAChRs, there are a number of candidate receptor systems within the retina which atropine may instead target, including that of serotonergic receptors. Therefore, this study investigated whether atropine’s protective effects against the development of form-deprivation myopia (FDM) can be disrupted by co-administration with the mAChR agonist muscarine, serotonin, or the serotonergic agonist 5-methoxytryptamine (5-MOT).
Chicks were divided between 9 groups (n=6 per group) and treated for 4 days: 1) age-matched untreated controls, 2) FDM only, 3) FDM plus 0.015mM atropine, 4) FDM plus 0.015mM atropine and 0.06mM muscarine, 5) FDM plus 0.015mM atropine and 0.6mM muscarine 6) FDM plus 0.015mM atropine and 0.05mM serotonin, 7) FDM plus 0.015mM atropine and 0.5mM serotonin, 8) FDM plus 0.015mM atropine and 0.05mM 5-MOT, and 9) FDM 0.015mM atropine and 0.5mM 5-MOT. For each drug treatment, a 10µL injection was made into the vitreous chamber once daily at 9am (lights on).
After 4 days of treatment, chicks administered atropine alone were significantly protected against the myopic refractive shift associated with FDM (FDM: -1.6±0.2D, FDM atropine: -0.2±0.4D, p<0.05). This protective effect was not inhibited by the co-administration of the mAChR agonist muscarine (0.06mM: 1.65±0.3D, p<0.001; 0.6mM: 0.5±0.3D, p<0.001), but was by co-administration of serotonin (0.05mM: -0.9±0.3D, p=0.181; 0.5mM: -1.0±0.4D, p=0.500) or the serotonergic agonist 5-MOT (0.05mM: -0.4±0.4D, p=0.266; 0.5mM: -1.1±0.5D, p=0.764). This same effect was observed in axial length measurements, with the protection afforded by atropine (FDM: 9.06±0.05mm, FDM atropine: 8.84±0.5mm, p<0.001) inhibited by both serotonin (0.05mM: 9.05±0.05mm, p=0.210; 0.5mM: 9.02±0.06mm, p=0.167) and 5-MOT (0.05mM: 8.94±0.05mm, p=0.198; 0.5mM: 8.98±0.05mm, p=0.584), but not by muscarine (0.06mM: 8.60±0.06mm, p<0.001; 0.6mM: 8.67±0.06mm, p<0.001).
Unlike muscarine, both serotonergic agents significantly disrupted atropine’s protection against the development of FDM, suggesting that atropine may elicit its anti-myopia effects through the inhibition of serotonergic receptors, rather than mAChRs.
This is a 2020 ARVO Annual Meeting abstract.
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