Light intensity and light/dark cycles regulate refractive development and myopia in mice through circadian rhythm-related genes.

PURPOSE: To investigate how different light/dark (L/D) cycles and light intensities influence refractive development and form-deprivation myopia (FDM) in mice, and to examine whether these phenotypes are accompanied by changes in retina/RPE circadian rhythm-related genes expression and dopamine levels.

METHODS

Three-week-old C57BL/6 J mice undergoing natural refractive development or monocular FDM (induced by translucent diffusers) were exposed for 4 weeks to three light intensities (10, 300, or 3000 lx) under four light/dark cycles. Refractive error, axial length (AL), Opn4, Cry1, Per3 expression, and dopamine levels in retina/RPE were assessed.

RESULTS

Extending photoperiod (from 6L/18D to 12L/12D, 18L/6D, or continuous light) induced significant myopic shifts (increased AL, decreased refraction) in natural refractive development mice at 300 lx and 3000 lx (both P < 0.001), but not at 10 lx. This shift correlated with decreased Opn4 and increased Cry1 and Per3 expression (P < 0.05). Notably, continuous light (CL) at 3000 lx significantly inhibited FDM progression (vs. other photoperiods P < 0.001), accompanied by elevated Opn4 and Cry1. Conversely, one week of CL at 10 lx transiently induced hyperopia in FDM mice. Retinal dopamine content showed no significant correlation with these refractive changes.

CONCLUSION

Light intensity and L/D cycles critically regulate refractive development and myopia progression in mice, with these effects showing stronger associations with alterations in circadian rhythm-related genes than with retinal dopamine levels. Continuous bright light (3000 lx) inhibits FDM, while dim light (10 lx) effects are photoperiod dependent. These findings suggest targeting optimized light exposure and circadian modulation as potential therapeutic strategies.