Purchase this article with an account.
Kate Thomson, Cindy Karouta, Regan Scott Ashby; Muscarinic-cholinergic and GABA antagonists appear to modulate eye growth independent of the dopaminergic system. Invest. Ophthalmol. Vis. Sci. 2018;59(9):754.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A number of pharmacological agents known to inhibit the development of form-deprivation myopia (FDM), such as atropine, pirenzepine and 1,2,5,6-tetrahydropyridine-4-yl-methylphosphinic acid (TPMPA)), have been reported to increase retinal dopamine release. Therefore, this study investigated whether each of these compounds induce their action through the dopaminergic system. To this end, we co-administered atropine, pirenzepine and TPMPA with the D2-like receptor antagonist spiperone which is known to inhibit the protective effects of dopamine against the development of experimental in the chicken.
Chicks were divided between 8 groups (min n=5 per group) and were treated for 4 days: 1) age-matched untreated controls, 2) FDM only, 3) FDM atropine, 4) FDM atropine and spiperone, 5) FDM pirenzepine, 6) FDM pirenzepine and spiperone, 7) FDM TPMPA, 8) FDM TPMPA and spiperone. Each compound was administered at a concentration shown previously to modulate eye growth (atropine 50mM; pirenzepine 170mM; TPMPA 18.6mM; spiperone 500µM). For each treatment, a 10µL injection was made into the vitreous chamber once daily at 9am (lights on).
After 4 days of treatment, all chicks administered single compounds were significantly protected against FDM (FDM: -1.3D; atropine: -0.08D, p=0.001; pirenzepine -0.12D, p=0.001; TPMPA: 0.74D, p<0.000). When co-administered with spiperone, this protective effect persisted for all three compounds (atropine: 0.16D, p=0.002; pirenzepine: -0.4D, P=0.008; TPMPA: 0.48D, p<0.000). The same effect was seen in axial length measurements, with a significantly shallower vitreal chamber depth in all drug-treated animals relative to FDM-only chicks (ANOVA, F(5,43)=7.267, p=0.000). No difference in anterior chamber depth (ANOVA, F(5,43)=0.541, p=0.707) or lens thickness (ANOVA, F(5,43)=0.980, p=0.441) was observed in any of the treatment groups.
Spiperone did not block the protective effects of atropine, pirenzepine or TPMPA; this suggests that these compounds modulate eye growth through a different pathway to that of the dopaminergic system, or that they act at a point downstream of dopamine. Despite being used at their standard effective concentrations, the number molecules of atropine, pirenzepine and TMPA present are well in excess of spiperone. Therefore, further work is required to determine that this is not simply a dosage effect.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only