The role of ipRGCs in ocular growth and myopia development

Liu, Ailin; Liu, Yunfeng; Wang, Ge; Shao, Yehong; Yu, Chen-Xi; Yang, Zhe; Zhou, Zhichao; Han, Xu; Gong, Xue; Qian, Kang-Wei; Wang, Liqin; Ma, Yuanyuan; Zhong, Yong-Mei; Weng, Shi-Jun; Yang, Xiong‐Li

doi:10.1126/sciadv.abm9027

Cited by 31 publications

(16 citation statements)

References 67 publications

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“…However, it has been proposed that these effects are due to activation of melanopsin (OPN4), which would not be activated by the red light used here. 34 If the red light-induced hyperopia is due to stimulation of longer wavelength cones and lack of stimulation of shorter wavelength cones, then we should expect the effect to be robust with changes in lighting intensity.…”

Section: Discussionmentioning

confidence: 99%

The effects of intensity, spectral purity and duty cycle on red light‐induced hyperopia in tree shrews

Gawne

Samal

She

2023

Ophthalmic Physiologic Optic

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IntroductionThere have recently been several clinical studies suggesting that brief periods of exposure to red light (repeated low‐level red light, ‘RLRL’) may produce a dramatic anti‐myopia effect, calling for further investigations into its therapeutic parameters. Unfortunately, many experimental species used in refractive studies develop myopia in response to this wavelength. Tree shrews are the only animal model other than rhesus monkeys that consistently exhibit hyperopic responses to ambient red light. Here, tree shrews were used to study the influence of the spectral purity, duty cycle and intensity of red light on its anti‐myopic effect.MethodsJuvenile tree shrews (Tupaia belangeri) were raised from 24 to 35 days after eye opening under ambient lighting that was: standard white colony fluorescent light; pure narrow band red light of either 600, 50–100 or 5 lux; red light that was diluted with 10% white light (by lux) or 50% white and 2 s of pure red light that alternated with 2 s of pure white light (50% duty cycle). Refractive measures were taken with a NIDEK ARK‐700 autorefractor and axial dimensions with a LenStar LS‐900 Axial Biometer.ResultsThe pro‐hyperopia effect of ambient red light was greatly reduced by even small amounts of concurrent white light ‘contamination’, but remained robust if 2‐s periods of pure white light alternated with 2 s of red. Finally, the hyperopic effect of red light was maintained at reduced luminance levels in the 50–100 lux range and only failed at 5 lux.ConclusionsThese results have implications for understanding the mechanisms by which ambient red light affects refractive development, and possibly also for clinical therapies using RLRL. Nevertheless, it remains to be determined if the mechanism of the current clinical RLRL therapy is the same as that operating on tree shrews in ambient red light.

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Section: Discussionmentioning

confidence: 99%

The effects of intensity, spectral purity and duty cycle on red light‐induced hyperopia in tree shrews

Gawne

Samal

She

2023

Ophthalmic Physiologic Optic

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“…It has been found that lncRNA Gm35369 might be related to myopia, and this lncRNA is mainly located in ganglion cells and horizontal cells [ 14 ]. Studies have reported that RGC alterations are associated with the occurrence and development of myopia, including changes in the number of RGCs, abnormal axonal projections and changes in protein expression in RGCs [ 19 – 22 , 38 ]. However, whether lncRNAs in RGCs are involved in the pathogenesis of myopia and the role of lncRNAs as ceRNAs in myopia are still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

Wang,

Lin,

Liu

et al. 2023

J Transl Med

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Background Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. Methods RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. Results The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. Conclusion We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

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“…More recently, studies have shown that light can also regulate nociception [25,26]. And finally, the light environment may exert an important role during development, including neonatal aversive behaviours [27,28], retinal vasculature development [29], ocular growth associated with myopia [30,31] and synapse formation in the brain [32]. Together, these data illustrate the wide-ranging influence of light on mammalian physiology and behaviour (Figure 1).…”

mentioning

confidence: 84%

“…Indeed, it is now apparent that, in mice, spectral signals originating from cones influence neural activity within the master circadian clock (the suprachiasmatic nucleus) and can modulate the timing and robustness of behavioural and physiological rhythms [6,89]. Finally, there are emerging data of a protective role of 'violet' (360-400nm) light against the development of myopia in mice and other species via as yet incompletely resolved mechanisms [30,31,[90][91][92][93][94].…”

Section: Species Specific Consideration Of 'Colour'mentioning

confidence: 99%

In the Eye of the Beholder: Measuring and Standardising Light for Laboratory Mammals

Lucas,

Allan,

brainard

et al. 2023

Preprint

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Light enables vision and exerts widespread effects on physiology and behaviour, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in a controlled physiological and behavioural state. Proper consideration of light during experimentation - both when it is explicitly employed as an independent variable and as a general feature of the environment - has the potential to provide more informative experimental designs and more reliable outcomes, contributing to Reduction and Refinement, helping to ensure more ethical animal use, and improving data quality. As such, it is unfortunate that ambient light for animals is typically quantified in units (lux) designed for human observers. We report the consensus views of an expert working group, with expertise spanning mammalian photobiology, neurobiology and animal husbandry and welfare, convened in February 2023 to agree upon metrics for light appropriate for non-human mammals and their application to improve animal welfare and the quality of animal research. We conclude that species-specific versions of the recently standardised a-opic metrology represent the best available approach to quantifying light. We provide methods for measuring these quantities; practical guidance for their implementation in husbandry and experimentation; and quantitative guidance on appropriate light exposure for laboratory mammals.

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The role of ipRGCs in ocular growth and myopia development

Cited by 31 publications

References 67 publications

The effects of intensity, spectral purity and duty cycle on red light‐induced hyperopia in tree shrews

The effects of intensity, spectral purity and duty cycle on red light‐induced hyperopia in tree shrews

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

In the Eye of the Beholder: Measuring and Standardising Light for Laboratory Mammals

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