Publications by authors named "Ethan D Buhr"

The cornea is the transparent tissue at the ocular surface that generates most of the refractive power of the eye. Due to its exposed location, the cornea is uniquely in danger of injury. Rapid and efficient healing is required for high-acuity vision.

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The choroid is the thin, vasculature-filled layer of the eye situated between the sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors in the retina. Illumination of the interior surface of the back of the eye (fundus) is a critical regulator of subretinal fluid homeostasis, which determines the overall shape of the eye, but it is also important for choroidal perfusion. Noted for having some of the highest blood flow rates in the body, the choroidal vasculature has been reported to lack intrinsic, intravascular pressure-induced (myogenic) autoregulatory mechanisms.

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  • There is an increasing interest in creating artificial light that activates specific retinal cells to help regulate circadian rhythms and improve overall well-being.
  • Researchers have focused on utilizing a photopigment called melanopsin but also discovered that color vision circuits in primates can transmit blue-yellow signals to these retinal cells.
  • A study found that using a specially designed light that alternates between short and long wavelengths resulted in a significant circadian phase shift in participants, outperforming traditional white light exposure in regulating sleep patterns.
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  • Researchers are exploring artificial lighting that can enhance circadian rhythms by targeting intrinsically photosensitive retinal ganglion cells (ipRGCs) to improve mood, sleep, and overall health.
  • The study highlights a new lighting design that stimulates color-opponent inputs to ipRGCs by alternating between short and long wavelengths, particularly focusing on short-wavelength sensitive cones.
  • Results show that a two-hour exposure to this specially designed light led to an average circadian phase advance of 1 hour and 20 minutes in participants, demonstrating its potential effectiveness over traditional white light in regulating circadian rhythms.
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Mammals maintain their internal body temperature within a physiologically optimal range. This involves the regulation of core body temperature in response to changing environmental temperatures and a natural circadian oscillation of internal temperatures. The preoptic area (POA) of the hypothalamus coordinates body temperature by responding to both external temperature cues and internal brain temperature.

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The presence of an endogenous circadian clock within most mammalian cells is associated with the amazing observation that within a given tissue, these clocks are largely in synchrony with each other. Different tissues use a variety of systemic or environmental cues to precisely coordinate the phase of these clocks. The cornea is a unique tissue in that it is largely isolated from the direct blood supply that most tissues experience, it is transparent to visible light, and it is exposed directly to environmental light and temperature.

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Most organisms contain self-sustained circadian clocks. These clocks can be synchronized by environmental stimuli, but can also oscillate indefinitely in isolation. In mammals this is true at the molecular level for the majority of cell types that have been examined.

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Animals have evolved light-sensitive G protein-coupled receptors, known as opsins, to detect coherent and ambient light for visual and nonvisual functions. These opsins have evolved to satisfy the particular lighting niches of the organisms that express them. While many unique patterns of evolution have been identified in mammals for rod and cone opsins, far less is known about the atypical mammalian opsins.

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In molecular biology laboratories, many tasks require fine motor control and high acuity vision. For example, lab technicians with visual impairment experience difficulty loading samples into the small wells of a horizontal agarose gel. We have developed a 3D-printable gel loading system which allows technicians with low-contrast vision to load gels correctly.

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Recently, we characterized blue light-mediated relaxation (photorelaxation) of airway smooth muscle (ASM) and implicated the involvement of opsin 3 (OPN3), an atypical opsin. In the present study, we characterized the cellular signaling mechanisms of photorelaxation. We confirmed the functional role of OPN3 in blue light photorelaxation using trachea from OPN3 null mice (maximal relaxation 52 ± 13% compared with wild-type mice 90 ± 4.

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The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light. In mice, OPN5 is a known photoreceptor in the retina and skin but is also expressed in the hypothalamic preoptic area (POA).

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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.

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Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes.

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Nearly all mammalian tissues have functional, autonomous circadian clocks, which free-run with non-24 h periods and must be synchronized (entrained) to the 24 h day. This entrainment mechanism is thought to be hierarchical, with photic input to the retina entraining the master circadian clock in the suprachiasmatic nuclei (SCN) and the SCN in turn synchronizing peripheral tissues via endocrine mechanisms. Here, we assess the function of a population of melanocyte precursor cells in hair and vibrissal follicles that express the photopigment neuropsin (OPN5).

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During mouse postnatal eye development, the embryonic hyaloid vascular network regresses from the vitreous as an adaption for high-acuity vision. This process occurs with precisely controlled timing. Here, we show that opsin 5 (OPN5; also known as neuropsin)-dependent retinal light responses regulate vascular development in the postnatal eye.

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Vision is a highly rhythmic function adapted to the extensive changes in light intensity occurring over the 24-hour day. This adaptation relies on rhythms in cellular and molecular processes, which are orchestrated by a network of circadian clocks located within the retina and in the eye, synchronized to the day/night cycle and which, together, fine-tune detection and processing of light information over the 24-hour period and ensure retinal homeostasis. Systematic or high throughput studies revealed a series of genes rhythmically expressed in the retina, pointing at specific functions or pathways under circadian control.

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We previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the 3'-UTR region: , which retains the endogenous 3'-UTR and , where the endogenous 3'-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of 3'-UTR, we analyzed circadian rhythms of mice. Interestingly, mice displayed more than threefold stronger amplitude in bioluminescence rhythms than mice, and also exhibited lengthened free-running periods (∼24.

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Article Synopsis
  • The study investigates whether the ciliary body and intraocular pressure (IOP) clocks in mice can adjust to light/dark cycles similar to how the retina does.
  • The research involves culturing iris-ciliary body complexes from specific mice strains and measuring their bioluminescence rhythm after exposure to light/dark cycles.
  • Results indicate that while certain opsin mRNAs are present in the iris-ciliary body, these structures do not directly respond to light/dark cycles, instead remaining synchronized to the overall behavioral rhythms of the mice.
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Circadian rhythms are self-sustained, approximately 24-h rhythms of physiology and behavior. These rhythms are entrained to an exactly 24-h period by the daily light-dark cycle. Remarkably, mice lacking all rod and cone photoreceptors still demonstrate photic entrainment, an effect mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs).

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  • Mure et al. (2016) explore how different mechanisms affect melanopsin, a nonvisual photoreceptor.
  • They identify two key factors: phosphorylation of the C-terminal intracellular region and a broader mechanism involving the entire C terminus.
  • These factors have opposing effects on the photoreceptor's response speed and how it senses light.
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  • Molecular circadian clocks in the mammalian retina can sync with environmental light cycles without relying on the brain's suprachiasmatic nuclei (SCN) or traditional photoreceptors like rods and cones.
  • The study found that short-wavelength light is crucial for this process, but does not depend on the previously known photopigments like S-pigment or encephalopsin.
  • Neuropsin (OPN5) is essential for photoentrainment in the retina and cornea, highlighting its previously underappreciated role as a light-sensing opsin.
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Synchronization of the mammalian master circadian pacemaker to the daily light/dark cycle is mediated exclusively through retinal photoreceptors. The mammalian retina itself is also a self-sustained circadian oscillator. Here we report that the retinal molecular circadian clock can be entrained by lighting cycles in vitro, but that rods, cones, and melanopsin (Opn4) are not required for this entrainment.

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Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases.

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