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Journal Title:

Investigative Ophthalmology and Visual Science


Volume 55, Number 10


Association for Research in Vision and Ophthalmology ARVO | 2014-10-01, Pages 6272-6279

Type of Work:

Article | Final Publisher PDF

Abstract: 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.

Keywords: Science and Technology - Life Sciences and Biomedicine - Ophthalmology - refractive development - myopia - rod photoreceptors - dopamine - FORM-DEPRIVATION MYOPIA - DOPAMINERGIC AMACRINE CELLS - STATIONARY NIGHT BLINDNESS - EYE GROWTH - REFRACTIVE DEVELOPMENT - MOUSE RETINA - OPTIC-NERVE - FOVEAL ABLATION - MESSENGER-RNA - KNOCKOUT MICE -

Autor: Han na Park, Seema B. Jabbar, Christopher C. Tan, Curran S. Sidhu, Jane Abey, Fazila Aseem, Gregor Schmid, Paul Iuvone, Machelle



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