Abstract
Purpose :
Atropine is one of the most widely used clinical interventions for myopia. However, its mechanism of action remains unclear. We have previously reported that atropine’s protective effects against form-deprivation myopia (FDM) can be disrupted by co-administration with serotonergic agonists (stimulants). This suggests a novel non-muscarinic mechanism by which this drug could function. This study wished to determine how conserved this mechanism is by investigating whether serotoninergic manipulation also prevents atropine’s efficacy in the other major form of experimental myopia (lens-induced myopia, LIM). Concurrently, this study investigated how topical atropine treatment affects retinal structure and function, with a view towards understanding its long-term safety.
Methods :
Experiment 1: chicks were divided between 3 groups (n=6 per group) and treated monocularly for 4 days: 1) LIM only, 2) LIM plus 0.15nmoles atropine daily, and 3) LIM plus 0.15nmoles atropine and 0.5nmoles serotonin daily. LIM development was measured using refraction (automated infrared photoretinoscopy) and axial length (A-scan ultrasonography). Experiment 2: 10 mice were treated with topical 1% w/v atropine (30 minutes before recordings (n=5) or once daily for 2 weeks (n=5)) before electoretinograms (ERGs) were measured.
Results :
Experiment 1 (atropine efficacy): after 4 days, chicks treated with atropine alone were significantly protected against the axial elongation and myopic refractive shift associated with LIM (~65%, p<0.05). This protection was significantly lost by serotonergic stimulation (p<0.05). Experiment 2 (changes in retinal function): atropine significant altered all ERG parameters at all measurement points over a 2 week treatment period (A-wave, B-wave and oscillatory potential 2; observed as a decrease in amplitude and increase in latency; p<0.05).
Conclusions :
Like that previously observed for FDM, co-administration with serotonergic agonists significantly disrupted atropine’s protection against the development of LIM. This suggests that the anti-myopic effects of atropine are conserved across multiple models of growth manipulation and, at least in part, brought about through the inhibition of serotonergic receptor activity. This study also found that atropine induces significant changes in ERG responses. The potential safety implications of such functional changes warrants investigation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.