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Violet light suppresses lens-induced myopia via neuropsin (OPN5) in mice.

ABSTRACT: Myopia has become a major public health concern, particularly across much of Asia. It has been shown in multiple studies that outdoor activity has a protective effect on myopia. Recent reports have shown that short-wavelength visible violet light is the component of sunlight that appears to play an important role in preventing myopia progression in mice, chicks, and humans. The mechanism underlying this effect has not been understood. Here, we show that violet light prevents lens defocus-induced myopia in mice. This violet light effect was dependent on both time of day and retinal expression of the violet light sensitive atypical opsin, neuropsin (OPN5). These findings identify Opn5-expressing retinal ganglion cells as crucial for emmetropization in mice and suggest a strategy for myopia prevention in humans.

SUBMITTER: Jiang X

PROVIDER: S-EPMC8179197 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Violet light suppresses lens-induced myopia via neuropsin (OPN5) in mice.

Jiang Xiaoyan X Pardue Machelle T MT Mori Kiwako K Ikeda Shin-Ichi SI Torii Hidemasa H D'Souza Shane S Lang Richard A RA Kurihara Toshihide T Tsubota Kazuo K

Proceedings of the National Academy of Sciences of the United States of America 20210601 22

Myopia has become a major public health concern, particularly across much of Asia. It has been shown in multiple studies that outdoor activity has a protective effect on myopia. Recent reports have shown that short-wavelength visible violet light is the component of sunlight that appears to play an important role in preventing myopia progression in mice, chicks, and humans. The mechanism underlying this effect has not been understood. Here, we show that violet light prevents lens defocus-induced ...[more]

PMID: 34031241

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Short-Wavelength (Violet) Light Protects Mice From Myopia Through Cone Signaling.

Project description:Purpose:Exposure to short-wavelength light influences refractive development and inhibits myopic development in many animal models. Retinal mechanisms underlying this response remain unknown. This study used a mouse model of lens-induced myopia to evaluate the effect of different wavelength light on refractive development and dopamine levels in the retina. A possible retinal pathway is tested using a mutant mouse with dysfunctional cones. Methods:Wild-type C57BL/6J (WT) and ALS/LtJ/Gnat2cpfl3 (Gnat2-/-) mice were exposed to one of three different light conditions beginning at postnatal day 28: broad-spectrum "white" (420-680 nm), medium wavelength "green" (525 ± 40 nm), and short wavelength "violet" (400 ± 20 nm). One-half of the mice received hyperopic lens defocus. All mice were exposed to the light for 4 weeks; animals were measured weekly for refractive error and axial parameters. Retinal dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid were measured by HPLC. Results:In WT mice, short-wavelength violet light induced hyperopia and violet light inhibited lens-induced myopia when compared with mice exposed to white light. Hyperopia could be attributed to shallower vitreous chambers in WT animals. There were no changes in the levels of dopamine or its metabolite. In Gnat2-/- mice, violet light did not induce hyperopia or inhibit lens-induced myopia. Conclusions:These findings show that short-wavelength light slows refractive eye growth, producing hyperopic responses in mice and inhibiting lens-induced myopia. The lack of inhibition in mice with dysfunctional cones suggests that cone signaling plays a role in the hyperopic response to short-wavelength (violet) light.

| S-EPMC7326482 | biostudies-literature

Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed Murine Skin.

Project description: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). Organotypic cultures of murine outer ear and vibrissal skin entrain to a light-dark cycle ex vivo, requiring cis-retinal chromophore and Opn5 gene function. Short-wavelength light strongly phase shifts skin circadian rhythms ex vivo via an Opn5-dependent mechanism. In vivo, the normal amplitude of Period mRNA expression in outer ear skin is dependent on both the light-dark cycle and Opn5 function. In Opn4-/-; Pde6brd1/rd1 mice that cannot behaviorally entrain to light-dark cycles, the phase of skin-clock gene expression remains synchronized to the light-dark cycle, even as other peripheral clocks remain phase-locked to the free-running behavioral rhythm. Taken together, these results demonstrate the presence of a direct photic circadian entrainment pathway and direct light-response elements for clock genes in murine skin, similar to pathways previously described for invertebrates and certain non-mammalian vertebrates.

| S-EPMC6814305 | biostudies-literature

Retinal patterns and the cellular repertoire of neuropsin (Opn5) retinal ganglion cells.

Project description:Obtaining a parts list of the sensory components of the retina is vital to understand the effects of light in behavior, health, and disease. Rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) are the best described photoreceptors in the mammalian retina, but recent functional roles have been proposed for retinal neuropsin (Opn5)-an atypical opsin. However, little is known about the pattern of Opn5 expression in the retina. Using cre (Opn5cre ) and cre-dependent reporters, we uncover patterns of Opn5 expression and find that Opn5 is restricted to retinal ganglion cells (RGCs). Opn5-RGCs are nonhomogenously distributed through the retina, with greater densities of cells located in the dorsotemporal quadrant. In addition to the local topology of these cells, using cre-dependent AAV viral tracing, we surveyed their central targets and found that they are biased towards image-forming and image-stabilizing regions. Finally, molecular and electrophysiological profiling reveal that Opn5-RGCs comprise previously defined RGC types that respond optimally to edges and object-motion (F-mini-ONs, HD2, HD1, LEDs, ooDSRGCs, etc.). Together, these data describe the second collection of RGCs that express atypical opsins in the mouse, and expand the roles of image-forming cells in retinal physiology and function.

| S-EPMC8969148 | biostudies-literature

Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression.

Project description:Prevalence of myopia is increasing worldwide. Outdoor activity is one of the most important environmental factors for myopia control. Here we show that violet light (VL, 360-400nm wavelength) suppresses myopia progression. First, we confirmed that VL suppressed the axial length (AL) elongation in the chick myopia model. Expression microarray analyses revealed that myopia suppressive gene EGR1 was upregulated by VL exposure. VL exposure induced significantly higher upregulation of EGR1 in chick chorioretinal tissues than blue light under the same conditions. Next, we conducted clinical research retrospectively to compare the AL elongation among myopic children who wore eyeglasses (VL blocked) and two types of contact lenses (partially VL blocked and VL transmitting). The data showed the VL transmitting contact lenses suppressed myopia progression most. These results suggest that VL is one of the important outdoor environmental factors for myopia control. Since VL is apt to be excluded from our modern society due to the excessive UV protection, VL exposure can be a preventive strategy against myopia progression.

| S-EPMC5233810 | biostudies-literature

Temporal bright light at low frequency retards lens-induced myopia in guinea pigs.

Project description:PurposeBright light conditions are supposed to curb eye growth in animals with experimental myopia. Here we investigated the effects of temporal bright light at very low frequencies exposures on lens-induced myopia (LIM) progression.MethodsMyopia was induced by application of -6.00 D lenses over the right eye of guinea pigs. They were randomly divided into four groups based on exposure to different lighting conditions: constant low illumination (CLI; 300 lux), constant high illumination (CHI; 8,000 lux), very low frequency light (vLFL; 300/8,000 lux, 10 min/c), and low frequency light (LFL; 300/8,000 lux, 20 s/c). Refraction and ocular dimensions were measured per week. Changes in ocular dimensions and refractions were analyzed by paired t-tests, and differences among the groups were analyzed by one-way ANOVA.ResultsSignificant myopic shifts in refractive error were induced in lens-treated eyes compared with contralateral eyes in all groups after 3 weeks (all P < 0.05). Both CHI and LFL conditions exhibited a significantly less refractive shift of LIM eyes than CLI and vLFL conditions (P < 0.05). However, only LFL conditions showed significantly less overall myopic shift and axial elongation than CLI and vLFL conditions (both P < 0.05). The decrease in refractive error of both eyes correlated significantly with axial elongation in all groups (P < 0.001), except contralateral eyes in the CHI group (P = 0.231). LFL condition significantly slacked lens thickening in the contralateral eyes.ConclusionsTemporal bright light at low temporal frequency (0.05 Hz) appears to effectively inhibit LIM progression. Further research is needed to determine the safety and the potential mechanism of temporal bright light in myopic progression.

| S-EPMC10655705 | biostudies-literature

The effects of ambient narrowband long-wavelength light on lens-induced myopia and form-deprivation myopia in tree shrews.

Project description:Here we examine the effects of ambient red light on lens-induced myopia and diffuser-induced myopia in tree shrews, small diurnal mammals closely related to primates. Starting at 24 days of visual experience (DVE), seventeen tree shrews were reared in red light (624 ± 10 or 634 ± 10 nm, 527-749 human lux) for 12-14 days wearing either a -5D lens (RL-5D, n = 5) or a diffuser (RLFD, n = 5) monocularly, or without visual restriction (RL-Control, n = 7). Refractive errors and ocular dimensions were compared to those obtained from tree shrews raised in broad-spectrum white light (WL-5D, n = 5; WLFD, n = 10; WL Control, n = 7). The RL-5D tree shrews developed less myopia in their lens-treated eyes than WL-5D tree shrews at the end of the experiment (-1.1 ± 0.9D vs. -3.8 ± 0.3D, p = 0.007). The diffuser-treated eyes of the RLFD tree shrews were near-emmetropic (-0.3 ± 0.6D, vs. -5.4 ± 0.7D in the WLFD group). Red light induced hyperopia in control animals (RL-vs. WL-Control, +3.0 ± 0.7 vs. +1.0 ± 0.2D, p = 0.02), the no-lens eyes of the RL-5D animals, and the no-diffuser eyes of the RLFD animals (+2.5 ± 0.5D and +2.3 ± 0.3D, respectively). The refractive alterations were consistent with the alterations in vitreous chamber depth. The lens-induced myopia developed in red light suggests that a non-chromatic cue could signal defocus to a less accurate extent, although it could also be a result of "form-deprivation" caused by defocus blur. As with previous studies in rhesus monkeys, the ability of red light to promote hyperopia appears to correlate with its ability to retard lens-induced myopia and form-deprivation myopia, the latter of which might be related to non-visual ocular mechanisms.

| S-EPMC10529043 | biostudies-literature

Integrative Transcriptome and Proteome Analyses Elucidate the Mechanism of Lens-Induced Myopia in Mice.

Project description:PurposeThe purpose of this study was to investigate the underlying molecular mechanism of lens-induced myopia (LIM) through transcriptome and proteome analyses with a modified mouse myopia model.MethodsFour-week-old C57BL/6J mice were treated with a homemade newly designed -25 diopter (D) lens mounting by a 3D printing pen before right eyes for 4 weeks. Refraction (RE) and axial dimensions were measured every 2 weeks. Retinas were analyzed by RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and STRING databases were used to identify significantly affected pathways in transcriptomic and proteomic data sets. Western blot was used to detect the expression of specific proteins.ResultsThe modified model was accessible and efficient. Mice displayed a significant myopic shift (approximately 8 D) following 4 weeks' of lens treatment. Through transcriptomics and proteomics analysis, we elucidated 175 differently expressed genes (DEGs) and 646 differentially expressed proteins (DEPs) between binoculus. The transcriptomic and proteomic data showed a low correlation. Going over the mRNA protein matches, insulin like growth factor 2 mRNA binding protein 1 (Igf2bp1) was found to be a convincing biomarker of LIM, which was confirmed by Western blot. RNA-seq and proteome profiling confirmed that these two "omics" data sets complemented one another in KEGG pathways annovation. Among these, metabolic and human diseases pathways were considered to be correlated with the LIM forming process.ConclusionsThe newly constructed LIM model provides a useful tool for future myopia research. Combining transcriptomic and proteomic analysis may potentially brighten the prospects of novel therapeutic targets for patients with myopia.

| S-EPMC10584019 | biostudies-literature

Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea.

Project description:The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength-sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin.

| S-EPMC4620855 | biostudies-other

Long-Wavelength-Filtered Light Transiently Inhibits Negative Lens-Induced Axial Eye Growth in the Chick Myopia Model.

Project description:PurposeEye growth and myopia development in chicks, and some other animal models, can be suppressed by rearing under near-monochromatic, short-wavelength blue light. We aimed to determine whether similar effects could be achieved using glass filters that transmit a broader range of short and middle wavelengths.MethodsOn day 6 or 7 post-hatch, 169 chicks were assigned to one of three monocular lens conditions (-10 D, +10 D, plano) and reared for 7 or 10 days under one of four 201-lux lighting conditions: (1) B410 long-wavelength-filtered light, (2) B460 long-wavelength-filtered light, (3) Y48 short-wavelength-filtered light, or (4) HA50 broadband light.ResultsAt 7 days, B410 (but not B460) long-wavelength-filtered light had significantly inhibited negative lens induced axial growth relative to Y48 short-wavelength-filtered light (mean difference in experimental eye = -0.249 mm; P = 0.006) and HA50 broadband light (mean difference = -0.139 mm; P = 0.038). B410 filters also inhibited the negative lens-induced increase in vitreous chamber depth relative to all other filter conditions. Corresponding changes in refraction did not occur, and biometric measurements in a separate cohort of chicks suggested that the axial dimension changes were transient and not maintained at 10 days.ConclusionsChromatic effects on eye growth can be achieved using filters that transmit a broad range of wavelengths even in the presence of strong cues for myopia development.Translational relevanceBroad-wavelength filters that provide a more "naturalistic" visual experience relative to monochromatic light have potential to alter myopia development, although the effects shown here were modest and transient and require exploration in further species.

| S-EPMC8411858 | biostudies-literature

Short Wavelength (Blue) Light Is Protective for Lens-Induced Myopia in Guinea Pigs Potentially Through a Retinoic Acid-Related Mechanism.

Project description:PurposeTo investigate the effect of short-wavelength light (SL) on guinea pigs with lens-induced myopia (LIM) and the possible retinoic acid (RA)-related mechanisms.MethodsTwo-week-old guinea pigs (n = 60) with monocular -5D lenses were reared under white light (WL, 580 lux) or SL (440 nm, 500 lux). The left eyes were uncovered as control. Refractive error (RE) and axial length (AL) were measured at baseline, one week, two weeks, and four weeks after intervention. Retinal RA was measured from four guinea pigs after two and four weeks of treatment with HPLC. Two-week-old guinea pigs (n = 52) with monocular -5D lens were fed with either RA or its synthesis inhibitor citral every third day in the morning, and half from each group were reared under WL or SL conditions. RE and AL were recorded at baseline and two and four weeks after intervention. Retinal RA was measured after four weeks of intervention.ResultsAt the end of treatment, guinea pigs exposed to SL were less myopic than to WL (2.06 ± 1.69D vs. -1.00 ± 1.88D), accompanied with shorter AL (P = 0.01) and less retinal RA (P = 0.02). SL reduced retinal RA even after exogenous RA supplementation (P = 0.02) and decelerated LIM compared to WL (1.66 ± 1.03D vs. -3.53 ± 0.90D). Citral slowed ocular growth, leading to similar RE in W+CI and S+CI groups (3.39 ± 1.65D vs. 5.25 ± 0.80D).ConclusionsOverall, SL reduced LIM in guinea pigs, even in those supplemented with oral RA, accompanied by reduced retinal RA levels. Oral RA accelerated eye elongation, but citral equally decelerated eye elongation under SL and WL with no significant retinal RA reduction.

| S-EPMC7817876 | biostudies-literature

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