Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

Sep 4, 2014Investigative ophthalmology & visual science

Eye growth driven by vision in mice depends on working rod cells

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Abstract

Gnat1(-/-) mice exhibited stable refractions at 7.39 ± 1.22 diopters, contrasting with wild-type mice that showed a myopic shift of 2.54 ± 0.77 diopters after form deprivation.

Wild-type mice started with a refractive state of 5.36 ± 0.68 diopters, becoming more hyperopic before plateauing at 7.78 ± 0.64 diopters.
Three weeks of form deprivation led to a significant myopic shift in wild-type mice but had no effect on Gnat1(-/-) mice.
Axial lengths increased with age for both genotypes, but the differences were not statistically significant.
DOPAC levels were significantly lower in Gnat1(-/-) mice throughout the study, with the DOPAC/dopamine ratio peaking earlier than in wild-type mice.
Dopamine levels did not show differences in response to form deprivation or between the two genotypes.

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PURPOSE: Proper refractive eye growth depends on several features of the visual image and requisite retinal pathways. In this study, we determined the contribution of rod pathways to normal refractive development and form deprivation (FD) myopia by testing Gnat1(-/-) mice, which lack functional rods due to a mutation in rod transducin-α.

METHODS: Refractive development was measured in Gnat1(-/-) (n = 30-36) and wild-type (WT) mice (n = 5-9) from 4 to 12 weeks of age. FD was induced monocularly from 4 weeks of age using head-mounted diffuser goggles (Gnat1(-/-), n = 9-10; WT, n = 7-8). Refractive state and ocular biometry were obtained weekly using a photorefractor, 1310 nm optical coherence tomography, and partial coherence interferometry. We measured retinal dopamine and its metabolite, DOPAC, using HPLC.

RESULTS: During normal development, the refractions of WT mice started at 5.36 ± 0.68 diopters (D) and became more hyperopic before plateauing at 7.78 ± 0.64 D. In contrast, refractions in Gnat1(-/-) mice were stable at 7.39 ± 1.22 D across all ages. Three weeks of FD induced a 2.54 ± 0.77 D myopic shift in WT mice, while Gnat1(-/-) mice did not respond to FD at any age. Axial lengths of Gnat1(-/-) and WT mice increased with age, but differences between genotypes or with goggling did not reach statistical significance and fell within the precision of the instruments. The DOPAC levels were significantly lower in Gnat1(-/-) mice from 2 to 12 weeks of age with DOPAC/dopamine ratio peaking earlier in Gnat1(-/-) compared to WT mice. No differences in dopamine were seen in response to FD or between genotypes.

CONCLUSIONS: Functional rod photoreceptors are critical to normal refractive development and the response to FD in mice. Dopamine levels may not directly modulate the refractive state of the mouse eye, but tonic levels of dopamine during development may determine susceptibility to myopia.

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Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

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