Dataset Information

Wounding Induces Facultative Opn5-Dependent Circadian Photoreception in the Murine Cornea.

ABSTRACT: Purpose:Autonomous molecular circadian clocks are present in the majority of mammalian tissues. These clocks are synchronized to phases appropriate for their physiologic role by internal systemic cues, external environmental cues, or both. The circadian clocks of the in vivo mouse cornea synchronize to the phase of the brain's master clock primarily through systemic cues, but ex vivo corneal clocks entrain to environmental light cycles. We evaluated the underlying mechanisms of this difference. Methods:Molecular circadian clocks of mouse corneas were evaluated in vivo and ex vivo for response to environmental light. The presence of opsins and effect of genetic deletion of opsins were evaluated for influence on circadian photoresponses. Opn5-expressing cells were identified using Opn5Cre;Ai14 mice and RT-PCR, and they were characterized using immunocytochemistry. Results:Molecular circadian clocks of the cornea remain in phase with behavioral circadian locomotor rhythms in vivo but are photoentrainable in tissue culture. After full-thickness incision or epithelial debridement, expression of the opsin photopigment Opn5 is induced in the cornea in a subset of preexisting epithelial cells adjacent to the wound site. This induction coincides with conferral of direct, short-wavelength light sensitivity to the circadian clocks throughout the cornea. Conclusions:Corneal circadian rhythms become photosensitive after wounding. Opn5 gene function (but not Opn3 or Opn4 function) is necessary for induced photosensitivity. These results demonstrate that opsin-dependent direct light sensitivity can be facultatively induced in the murine cornea.

SUBMITTER: Diaz NM

PROVIDER: S-EPMC7415322 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Wounding Induces Facultative Opn5-Dependent Circadian Photoreception in the Murine Cornea.

Díaz Nicolás M NM Lang Richard A RA Van Gelder Russell N RN Buhr Ethan D ED

Investigative ophthalmology & visual science 20200601 6

<h4>Purpose</h4>Autonomous molecular circadian clocks are present in the majority of mammalian tissues. These clocks are synchronized to phases appropriate for their physiologic role by internal systemic cues, external environmental cues, or both. The circadian clocks of the in vivo mouse cornea synchronize to the phase of the brain's master clock primarily through systemic cues, but ex vivo corneal clocks entrain to environmental light cycles. We evaluated the underlying mechanisms of this diff ...[more]

PMID: 32543667

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Project description:PurposeMice 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.MethodsNonvisual photoreception (pupillary light responses, circadian entrainment, and in vitro sensitivity of intrinsically photosensitive retinal ganglion cells) were studied in wild-type, rd/rd, and circadian clock-mutant mice with and without rd/rd mutation.ResultsLoss 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.ConclusionsThe 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.

Dataset Information

Wounding Induces Facultative Opn5-Dependent Circadian Photoreception in the Murine Cornea.

Publications

Wounding Induces Facultative Opn5-Dependent Circadian Photoreception in the Murine Cornea.

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