Lack of cone mediated retinal function increases susceptibility to form-deprivation myopia in mice

• Type of Material: Article
• Authors: Ranjay Chakraborty, Emory University; Victoria Yang, Atlanta VA Medical Center; Han na Park, Emory University; Erica G. Landis, Emory University; Susov Dhakal, Emory University; Michael A. Bergen, Emory University; Paul Iuvone, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2019-03-01
• Publisher: Elsevier Science Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2018.12.021
• Title of Journal or Parent Work: Experimental Eye Research
• Volume: 180
• Start Page: 226
• End Page: 230
• Grant/Funding Information: This project was supported by the National Institutes of Health (NIH R01 EY016435, NIH R01 EY004864, NIH P30 EY006360); Department of Veterans Affairs (Rehabilitation R&D Service Research Career Scientist Award to MTP); Research to Prevent Blindness (Departmental Award).
• Keywords: Mouse; Science & Technology; Eye growth; Ocular growth; Optic nerve; Refractive error; Emmetropization; Rod pathways; Ophthalmology; Life Sciences & Biomedicine; Mouse model; Cone photoreceptors; Dopamine; Form-deprivation; Refractive development; Gnat2; Bipolar cells; Alpha subunit
• Research Categories: Health Sciences, Opthamology; Health Sciences, Pharmacology; Biology, Neuroscience; Engineering, Biomedical; Health Sciences, Rehabilitation and Therapy

Abstract

Retinal photoreceptors are important in visual signaling for normal eye growth in animals. We used Gnat2 cplf3/cplf3 (Gnat2 −/− ) mice, a genetic mouse model of cone dysfunction to investigate the influence of cone signaling in ocular refractive development and myopia susceptibility in mice. Refractive development under normal visual conditions was measured for Gnat2 −/− and age-matched Gnat2 +/+ mice, every 2 weeks from 4 to 14 weeks of age. Weekly measurements were performed on a separate cohort of mice that underwent monocular form-deprivation (FD) in the right eye from 4 weeks of age using head-mounted diffusers. Refraction, corneal curvature, and ocular biometrics were obtained using photorefraction, keratometry and optical coherence tomography, respectively. Retinas from FD mice were harvested, and analyzed for dopamine (DA) and 3,4-dihydroxyphenylacetate (DOPAC) using high-performance liquid chromatography. Under normal visual conditions, Gnat2 +/+ and Gnat2 −/− mice showed similar refractive error, axial length, and corneal radii across development (p > 0.05), indicating no significant effects of the Gnat2 mutation on normal ocular refractive development in mice. Three weeks of FD produced a significantly greater myopic shift in Gnat2 −/− mice compared to Gnat2 +/+ controls (−5.40 ± 1.33 D vs −2.28 ± 0.28 D, p = 0.042). Neither the Gnat2 mutation nor FD altered retinal levels of DA or DOPAC. Our results indicate that cone pathways needed for high acuity vision in primates are not as critical for normal refractive development in mice, and that both rods and cones contribute to visual signalling pathways needed to respond to FD in mammalian eyes.