Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

• Type of Material: Article
• Authors: Han na Park, Emory University; Seema B. Jabbar, Emory University; Christopher C. Tan, Emory University; Curran S. Sidhu, Emory University; Jane Abey, Emory University; Fazila Aseem, Emory University; Gregor Schmid, Emory University; Paul Iuvone, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2014-10-01
• Publisher: Association for Research in Vision and Ophthalmology (ARVO)
• Publication Version: Final Published Version
• Copyright Statement: © 2014 The Association for Research in Vision and Ophthalmology, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.14-14648
• Title of Journal or Parent Work: Investigative Ophthalmology & Visual Science
• ISSN: 0146-0404
• Volume: 55
• Issue: 10
• Start Page: 6272
• End Page: 6279
• Grant/Funding Information: Supported by the National Institutes of Health (NIH) Grants R01 EY016435 (MTP), P30 EY006360 (PMI), and R01 EY004864 (PMI); a Department of Veterans Affairs Rehabilitation R&D Service Research Career Scientist Award (MTP), and an unrestricted departmental grant and a Senior Scientific Investigator Award from the Research to Prevent Blindness (PMI).
• Keywords: Science & Technology; dopamine; MOUSE RETINA; FOVEAL ABLATION; myopia; MESSENGER-RNA; refractive development; Life Sciences & Biomedicine; EYE GROWTH; FORM-DEPRIVATION MYOPIA; DOPAMINERGIC AMACRINE CELLS; OPTIC-NERVE; rod photoreceptors; REFRACTIVE DEVELOPMENT; STATIONARY NIGHT BLINDNESS; KNOCKOUT MICE; Ophthalmology
• Research Categories: Health Sciences, Opthamology

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.