Removal of clock gene Bmal1 from the retina affects retinal development and accelerates cone photoreceptor degeneration during aging

• Type of Material: Article
• Authors: Kenkichi Baba, Morehouse School of Medicine; Ilaria Piano, Morehouse School of Medicine; Polina Lyuboslavsky, Emory University; Micah A. Chrenek, Emory University; Jana T. Sellers, Emory University; Shuo Zhang, Emory University; Claudia Gargini, University of Pisa; Li He, Emory University; Gianluca Tosini, Emory University; P Michael Iuvone, Emory University
• Language: English
• Date: 2018-12-18
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2018 National Academy of Sciences. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1808137115
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 115
• Issue: 51
• Start Page: 13099
• End Page: 13104
• Grant/Funding Information: This work was supported by the National Institutes of Health Grants GM116760 (to K.B.), R01EY026291 (to G.T.), 5U54NS083932 (to Morehouse School of Medicine), R01EY004864, R01EY027711, and P30EY006360 (to P.M.I.); the Abraham J. and Phyllis Katz Foundation; and by an unrestricted Emory Department of Ophthalmology grant from Research to Prevent Blindness.
• Keywords: DOPAMINE; aging; CIRCADIAN CLOCK; RHYTHMS; retina; Science & Technology - Other Topics; cone photoreceptor; COMPONENT; circadian rhythm; ADULT; Science & Technology; development; MOUSE RETINA; Multidisciplinary Sciences
• Research Categories: Health Sciences, Opthamology; Biology, Genetics

Abstract

The mammalian retina contains an autonomous circadian clock system that controls many physiological functions within this tissue. Previous studies on young mice have reported that removal of the key circadian clock gene Bmal1 from the retina affects the circadian regulation of visual function, but does not affect photoreceptor viability. Because dysfunction in the circadian system is known to affect cell viability during aging in other systems, we compared the effect of Bmal1 removal from the retina on visual function, inner retinal structure, and photoreceptor viability in young (1 to 3 months) and aged (24 to 26 months) mice. We found that removal of Bmal1 from the retina significantly affects visual information processing in both rod and cone pathways, reduces the thickness of inner retinal nuclear and plexiform layers, accelerates the decline of visual functions during aging, and reduces the viability of cone photoreceptors. Our results thus suggest that circadian clock dysfunction, caused by genetic or other means, may contribute to the decline of visual function during development and aging.