Abstract
Purpose :
Injections of the D2 dopamine agonist quinpirole prevent the development of negative-lens-induced myopia in chicks by inhibiting ocular growth. Because retinal dopamine levels fluctuate in a diurnal rhythm, being highest during the day, and because they depend on light intensity, it is possible that the growth inhibiting effects of quinpirole might differ depending on when it is administered. We tested this hypothesis.
Methods :
12-d old chicks wore monocular -10D spectacle lenses (image behind the retina; hyperopic defocus) for 5 days. The lens-wearing eye was injected intravitreally, once daily, with 20 µl of quinpirole (10 nmoles) or 20 µl saline, at the following times: 7:00 am (drug, n=12; saline, n=5), 12:00 pm (drug, n=6; saline, n=6), or 7:00 pm (drug n=18; saline n=12). Because there were no between-group differences in the saline controls, these data were combined. Ocular dimensions were measured using high frequency A-scan ultrasonography on day 1, and again on day 5. Refractions were measured on day 5 using a Hartinger’s refractometer.
Results :
We found that injections at noon only were effective at inhibiting myopia (ANOVA p=0.002; drug vs saline: -1.1 D vs -4.3 D; post-hoc Bonferroni p=0.03). Injections at 7am and 7pm had no effect (-2.6 and -3.3 vs -4.3; p>0.5). The myopia inhibition was the result of inhibiting axial growth (change in axial length: ANOVA p=0.003; drug vs saline: 241 vs 485 µm; post-hoc Bonferroni p=0.007); there was no such inhibition in either the 7 am or 7 pm injection groups (363 µm and 483 µm vs 485 µm; p=0.18; 0.99 respectively). The changes in vitreous chamber depth were consistent with that of axial length for all groups. Finally, choroids in the noon injection group, which inhibited eye growth, showed less thinning in response to the negative lens-induced defocus than did those of the 7 am group (ANOVA p=0.02; -27 vs -127 µm; post-hoc Bonferroni p=0.053), but did not differ from the thinning in the 7 pm group (-49 µm; p>0.5).
Conclusions :
Quinpirole is not effective at inhibiting ocular growth when given first thing in the morning, or late in the day, indicating that there is a diurnal rhythm in susceptibility to this drug. This supports the possibility that there are differential susceptibilities for other, more clinically-relevant drugs, such as low-dose atropine.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.