Altered ocular parameters from circadian clock gene disruptions

• Type of Material: Article
• Authors: Richard A. Stone, University of Pennsylvania; Alice M. McGlinn, University of Pennsylvania; Ranjay Chakraborty, Emory University; Duk Cheon Lee, Emory University; Victoria Yang, Atlanta VA Medical Center; Ayman Elmasri, Emory University; Erica Landis, Emory University; James Shaffer, University of Pennsylvania; P Michael Iuvone, Emory University; Xiangzhong Zheng, University of Pennsylvania; Amita Sehgal, University of Pennsylvania; Machelle Pardue, Emory University
• Language: English
• Date: 2019-06-18
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Stone et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0217111
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 14
• Issue: 6
• Start Page: e0217111
• End Page: e0217111
• Grant/Funding Information: This research was supported by National Institutes of Health grants R01 EY022342 (RAS), R01 EY016435 (MTP), R01 EY004864 (PMI), R01 EY027711 (PMI), P30 EY001583, P30 EY006360; Department of Veterans Affairs (MTP); Rehab R&D Service Research Career Scientist Award (MTP); the Paul and Evanina Bell Mackall Foundation Trust (RAS); Research to Prevent Blindness and the Howard Hughes Medical Institute (AS).
• Keywords: RETINAL THICKNESS; SCHEMATIC EYE; EXPRESSION; Science & Technology - Other Topics; EXPERIMENTAL MYOPIA; Science & Technology; DOPAMINE; MOUSE; CHOROIDAL THICKNESS; AXIAL LENGTH; MAMMALIAN RETINA; REFRACTIVE DEVELOPMENT; Multidisciplinary Sciences
• Research Categories: Health Sciences, Opthamology; Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

The pathophysiology of refractive errors is poorly understood. Myopia (nearsightedness) in particular both blurs vision and predisposes the eye to many blinding diseases during adulthood. Based on past findings of diurnal variations in the dimensions of the eyes of humans and other vertebrates, altered diurnal rhythms of these ocular dimensions with experimentally induced myopia, and evolving evidence that ambient light exposures influence refractive development, we assessed whether disturbances in circadian signals might alter the refractive development of the eye. In mice, retinal-specific knockout of the clock gene Bmal1 induces myopia and elongates the vitreous chamber, the optical compartment separating the lens and the retina. These alterations simulate common ocular findings in clinical myopia. In Drosophila melanogaster, knockouts of the clock genes cycle or period lengthen the pseudocone, the optical component of the ommatidium that separates the facet lens from the photoreceptors. Disrupting circadian signaling thus alters optical development of the eye in widely separated species. We propose that mechanisms of myopia include circadian dysregulation, a frequent occurrence in modern societies where myopia also is both highly prevalent and increasing at alarming rates. Addressing circadian dysregulation may improve understanding of the pathogenesis of refractive errors and introduce novel therapeutic approaches to ameliorate myopia development in children.