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Author Notes:

Richard A. Stone: stone@pennmedicine.upenn.edu

Conceptualization: Richard A. Stone, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T. Pardue; Formal analysis: Ranjay Chakraborty, James Shaffer, Machelle T. Pardue; Funding acquisition: Richard A. Stone, P. Michael Iuvone, Amita Sehgal, Machelle T. Pardue; Investigation: Alice M. McGlinn, Ranjay Chakraborty, Duk Cheon Lee, Ayman Elmasri, Erica Landis, Xiangzhong Zheng; Methodology: Richard A. Stone, P. Michael Iuvone, Xiangzhong Zheng, Machelle T. Pardue; Project administration: Richard A. Stone, Ranjay Chakraborty, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T. Pardue; Resources: Richard A. Stone, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T. Pardue; Supervision: Richard A. Stone, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T. Pardue; Validation: Richard A. Stone, Alice M. McGlinn, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T. Pardue; Visualization: Richard A. Stone, Victoria Yang, James Shaffer, Machelle T. Pardue. Writing – original draft: Richard A. Stone, Machelle T. Pardue; Writing – review & editing: Richard A. Stone, Alice M. McGlinn, Ranjay Chakraborty, Erica Landis, James Shaffer, P. Michael Iuvone, Xiangzhong Zheng, Amita Sehgal, Machelle T.

The authors thank Dr. Maureen G. Maguire for statistical consultation; Jiayan Huang for assistance in the preliminary data analysis; Micah A. Chrenek and Brooke Still for mouse breeding and genotyping; and Mary Leonard for assistance with illustrations.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • AXIAL LENGTH
  • REFRACTIVE DEVELOPMENT
  • EXPERIMENTAL MYOPIA
  • CHOROIDAL THICKNESS
  • RETINAL THICKNESS
  • MAMMALIAN RETINA
  • SCHEMATIC EYE
  • DOPAMINE
  • MOUSE
  • EXPRESSION

Altered ocular parameters from circadian clock gene disruptions

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Journal Title:

PLoS ONE

Volume:

Volume 14, Number 6

Publisher:

, Pages e0217111-e0217111

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2019 Stone et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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