Melanopsin knock-out mice have abnormal refractive development and increased susceptibility to form-deprivation myopia.

Abstract

Purpose: Melanopsin, a photopigment in intrinsically photosensitive retinal ganglion cells (ipRGCs), is involved in regulating visual signaling, retinal dopaminergic cell activity, and circadian activity. Here, we examined the contribution of melanopsin to normal refractive development and to visual form-deprivation (FD) in a mutant mouse lacking melanopsin (Opn4^-/-).

Methods: Refractive development of Opn4^-/- and age-matched wild-type (WT) mice, both on mixed C57BL/6 and 129S1/Sv background, were measured every 2 weeks from 4 to 16 weeks of age. Weekly measurements were performed on a separate cohort of mice that underwent monocular FD in the right eye from 4 weeks of age using head-mounted diffuser goggles. Refraction, corneal curvature, and ocular biometry were obtained using photorefraction, keratometry and 1310 nm spectral-domain optical coherence tomography.

Results: Under normal visual conditions, Opn4^-/- mice (n=10) were significantly more myopic than WT mice (n=10) at early ages (mean refractive error at 4 weeks, Opn4^-/-: -3.56 ± 0.35 D; WT: +0.94 ± 0.35 D, p<0.05), and they became relatively more hyperopic than the WT mice by the end of 16 weeks (Opn4^-/-: +6.53 ± 0.25 D, WT: +4.52 ± 0.64 D, p<0.05). The axial length of Opn4^-/- mice (mean at 12 weeks, 3.29 ± 0.01 mm) was significantly shorter (p<0.001) than that of WT animals (3.35 ± 0.01 mm). After 3 weeks of FD, goggled Opn4^-/- mice (n=6) showed a significant myopic shift (difference between the right and left eyes) of -4.08 ± 0.89 D compared to non-goggled controls (n=6, + 0.43 ± 0.52 D, p<0.05). No significant refractive shift was observed in WT mice goggled for 3 weeks (-1.65 ± 0.65 D). Also, Opn4^-/- mice showed a significant increase (p<0.05) in axial length with FD at 3 weeks (difference of right and left eyes) of 0.03 ± 0.01 mm in comparison with WT animals (-0.01 ± 0.004 mm). There were no significant differences in corneal curvatures of Opn4^-/- and WT mice under either normal or FD conditions.

Conclusions: Our findings suggest that melanopsin signaling pathways contribute to normal refractive development, and the development of FD myopia in mice. Future studies are needed to determine other mechanisms underlying abnormal ocular development in Opn4^-/- mice, and the extent to which these findings reflect an interaction of refractive development and circadian biology.