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

Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13099-13104. doi: 10.1073/pnas.1808137115. Epub 2018 Nov 29.


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.

Keywords: aging; circadian rhythm; cone photoreceptor; development; retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / physiology*
  • Aging / metabolism
  • Aging / pathology*
  • Animals
  • Circadian Clocks
  • Circadian Rhythm*
  • Gene Expression Regulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Retina / metabolism
  • Retina / pathology*
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Cone Photoreceptor Cells / pathology*
  • Vision, Ocular*


  • ARNTL Transcription Factors
  • Arntl protein, mouse