Abstract
Purpose :
Myopia has been associated with late chronotype, characterised by a preference for later bedtimes and wake-up times. However, the causality of this association remains unclear. One factor influencing chronotype is the intrinsic circadian clock period length, where a longer period leads to a phase delay and, consequently, a late chronotype. Here, we employ environmental light manipulations in mice to determine whether lengthening the circadian period is causally related to the development of myopic refractive error.
Methods :
From postnatal day (P) 28, male and female C57BL/6J mice were subjected to different light-dark cycles: control mice were housed in a standard 12:12-h light-dark (LD) cycle (T24) and experimental mice in an 11:11-h (T22) or a 13:13-h (T26) LD cycle (n=5-6 per group). Refractive error (RE), corneal radius of curvature (CRC), and ocular axial parameters, including axial length (AL), vitreous chamber depth (VCD), anterior chamber depth (ACD) and lens thickness (LT), were measured weekly from P28 (baseline) until P56. Data were analysed using two-way ANOVA with Dunnett’s post-hoc tests.
Results :
At baseline, there were no differences in any of the measured parameters between the three groups. The length of the light-dark cycle significantly influenced the development of RE and CRC (two-way ANOVA interaction effect T cycle x postnatal day, p = 0.0003 and p = 0.048, respectively). Mice housed at T26 developed more myopic RE and steeper CRC compared to control mice. RE was more myopic in mice housed in T26 compared to T24 at P49 (mean ± SEM, T24: 13.5 ± 1.0 dioptres [D], T26: 6.2 ± 1.0 D, p = 0.001) and P56 (T24: 11.3 ± 0.8 D, T26: 5.0 ± 1.7 D, p = 0.021). RE and CRC did not differ between mice housed at T24 and T22. Light-dark cycle length did not affect the development of AL, VCD, ACD and LT.
Conclusions :
This study demonstrates that artificially lengthening the circadian period in mice results in more myopic refractions compared to the standard T24 light cycle. These findings suggest that the extended circadian period observed in individuals with a late chronotype may contribute to aspects of their refractive development. However, the underlying mechanisms of this phenomenon remain to be uncovered.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.