Effect of circadian clock gene mutations on nonvisual photoreception in the mouse

Leah Owens, Ethan Buhr, Daniel Tu, Tamara L. Lamprecht, Janet Lee, Russell N. van Gelder

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PURPOSE. Mice lacking rods and cones retain pupillary light reflexes that are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is necessary and sufficient for this nonvisual photoreception. The mammalian inner retina also expresses the potential blue light photopigments cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal degenerate mice, suggesting a role for cryptochrome in inner retinal photoreception. METHODS. Nonvisual photoreception (pupillary light responses, circadian entrainment, and in vitro sensitivity of intrinsically photosensitive retinal ganglion cells) were studied in wildtype, rd/rd, and circadian clock-mutant mice with and without rd/rd mutation. RESULTS. Loss of cryptochrome in retinal degenerate mice reduces the sensitivity of the pupillary light response at all wavelengths but does not alter the form of the action spectrum, suggesting that cryptochrome does not function as a photopigment in the inner retina. The authors compounded the rd/rd retinal degeneration mutation with mutations in other essential circadian clock genes, mPeriod and Bmal1. Both mPeriod1 -/-; mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice showed significantly lower pupillary light sensitivity than rd/rd mice alone. A moderate amplitude (0.5 log) circadian rhythm of pupillary light responsiveness was observed in rd/rd mice. Multielectrode array recordings of ipRGC responses of mCryptochrome1 -/-;mCryptochrome2 -/- and mPeriod1 -/-; mPeriod2 -/- mice showed minimal sensitivity decrement compared with wild-type animals. mCryptochrome1 -/-;mCryptochrome2 -/-;rd/rd, mPeriod1 -/-;mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice all showed comparable weak behavioral synchronization to a 12-hour light/12-hour dark cycle. CONCLUSIONS. The effect of cryptochrome loss on nonvisual photoreception is due to loss of the circadian clock nonspecifically. The circadian clock modulates the sensitivity of nonvisual photoreception.

Original languageEnglish (US)
Pages (from-to)454-460
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Circadian Clocks
Cryptochromes
Mutation
Genes
Light
Photophobia
Retinal Ganglion Cells
Retina
Pupillary Reflex
Retinal Degeneration
Vertebrate Photoreceptor Cells
Wild Animals
Circadian Rhythm

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Effect of circadian clock gene mutations on nonvisual photoreception in the mouse. / Owens, Leah; Buhr, Ethan; Tu, Daniel; Lamprecht, Tamara L.; Lee, Janet; van Gelder, Russell N.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 1, 01.2012, p. 454-460.

Research output: Contribution to journalArticle

Owens, Leah ; Buhr, Ethan ; Tu, Daniel ; Lamprecht, Tamara L. ; Lee, Janet ; van Gelder, Russell N. / Effect of circadian clock gene mutations on nonvisual photoreception in the mouse. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 1. pp. 454-460.
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N2 - PURPOSE. Mice lacking rods and cones retain pupillary light reflexes that are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is necessary and sufficient for this nonvisual photoreception. The mammalian inner retina also expresses the potential blue light photopigments cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal degenerate mice, suggesting a role for cryptochrome in inner retinal photoreception. METHODS. Nonvisual photoreception (pupillary light responses, circadian entrainment, and in vitro sensitivity of intrinsically photosensitive retinal ganglion cells) were studied in wildtype, rd/rd, and circadian clock-mutant mice with and without rd/rd mutation. RESULTS. Loss of cryptochrome in retinal degenerate mice reduces the sensitivity of the pupillary light response at all wavelengths but does not alter the form of the action spectrum, suggesting that cryptochrome does not function as a photopigment in the inner retina. The authors compounded the rd/rd retinal degeneration mutation with mutations in other essential circadian clock genes, mPeriod and Bmal1. Both mPeriod1 -/-; mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice showed significantly lower pupillary light sensitivity than rd/rd mice alone. A moderate amplitude (0.5 log) circadian rhythm of pupillary light responsiveness was observed in rd/rd mice. Multielectrode array recordings of ipRGC responses of mCryptochrome1 -/-;mCryptochrome2 -/- and mPeriod1 -/-; mPeriod2 -/- mice showed minimal sensitivity decrement compared with wild-type animals. mCryptochrome1 -/-;mCryptochrome2 -/-;rd/rd, mPeriod1 -/-;mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice all showed comparable weak behavioral synchronization to a 12-hour light/12-hour dark cycle. CONCLUSIONS. The effect of cryptochrome loss on nonvisual photoreception is due to loss of the circadian clock nonspecifically. The circadian clock modulates the sensitivity of nonvisual photoreception.

AB - PURPOSE. Mice lacking rods and cones retain pupillary light reflexes that are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is necessary and sufficient for this nonvisual photoreception. The mammalian inner retina also expresses the potential blue light photopigments cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal degenerate mice, suggesting a role for cryptochrome in inner retinal photoreception. METHODS. Nonvisual photoreception (pupillary light responses, circadian entrainment, and in vitro sensitivity of intrinsically photosensitive retinal ganglion cells) were studied in wildtype, rd/rd, and circadian clock-mutant mice with and without rd/rd mutation. RESULTS. Loss of cryptochrome in retinal degenerate mice reduces the sensitivity of the pupillary light response at all wavelengths but does not alter the form of the action spectrum, suggesting that cryptochrome does not function as a photopigment in the inner retina. The authors compounded the rd/rd retinal degeneration mutation with mutations in other essential circadian clock genes, mPeriod and Bmal1. Both mPeriod1 -/-; mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice showed significantly lower pupillary light sensitivity than rd/rd mice alone. A moderate amplitude (0.5 log) circadian rhythm of pupillary light responsiveness was observed in rd/rd mice. Multielectrode array recordings of ipRGC responses of mCryptochrome1 -/-;mCryptochrome2 -/- and mPeriod1 -/-; mPeriod2 -/- mice showed minimal sensitivity decrement compared with wild-type animals. mCryptochrome1 -/-;mCryptochrome2 -/-;rd/rd, mPeriod1 -/-;mPeriod2 -/-;rd/rd and Bmal1 -/-;rd/rd mice all showed comparable weak behavioral synchronization to a 12-hour light/12-hour dark cycle. CONCLUSIONS. The effect of cryptochrome loss on nonvisual photoreception is due to loss of the circadian clock nonspecifically. The circadian clock modulates the sensitivity of nonvisual photoreception.

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