The interplay between form deprivation and dopamine signaling in regulating the expression of circadian rhythm-related genes in the retina of mice.

PURPOSE: To investigate short-term and long-term effect of form deprivation, interacted with dopamine, on the expression of circadian rhythm-related genes in the retina of mice.

METHODS

Circadian rhythm-related genes (Opn4, Bmal1, Clock, Cry1, Per1) were measured by qPCR at Zeitgeber time (ZT) = 0, 4, 8, 12, 16, 20 h (n = 10 animals/time point) within one day (n = 60) at baseline and 4 weeks (n = 60) in C57BL/6J mice with monocular form deprivation. Mice were randomly assigned to receive intraperitoneal injections of either dopamine agonist (6,7-ADTN hydrobromide, n = 60) or phosphate buffered saline (PBS, n = 60). Ocular parameters were measured at baseline and 4 weeks.

RESULTS

Form deprivation induced significant axial elongation (0.39 mm, p = 0.016) and myopic shift (-8.33 D, p < 0.001) at 4 weeks. Compared with the contralateral eye, the expression of Opn4 in the form-deprived eye significantly decreased at ZT = 0, 8, and 16 h at baseline and increased at ZT = 8 and 16 h at 4 weeks. Other circadian rhythm related-genes also exhibited time-dependent change. Intraperitoneal injections of dopamine agonist abolished time-dependent changes in Opn4 expression in form-deprived eye and reduced the changes in Opn4 expression over time in the contralateral eye (p = 0.028).

CONCLUSION

Form deprivation disturbed endogenous circadian rhythm signaling pathways in the retina both in the early stage and long term. Exogenous dopamine altered the expression of Opn4 and circadian rhythm-related genes, indicating a complex role of circadian rhythm in myopia development.