Circadian clock regulates tear secretion in the lacrimal gland

Vu, Chi Hoang Viet; Kawashima, Motoko; Nakamura, Wataru; Nakamura, Takahiro J.; Ohta, Michio

doi:10.1016/j.exer.2021.108524

Cited by 9 publications

(5 citation statements)

References 33 publications

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“… 22 The lacrimal glands maintain the health of the ocular surface by secreting an aqueous layer in the tear film of the eye together with many important chemicals, peptides, and proteins to lubricate and protect the ocular surface. Similar to other glands, 23 , 24 its secretion process is closely controlled by the body's circadian rhythm, including tear volume, 25 – 27 physical properties, 25 , 28 and chemical composition. 29 , 30 Any factor that interferes with the circadian rhythm of the extraorbital lacrimal glands (ELGs), such as jet lag, 31 hyperglycemia, 32 high fructose intake, 33 and aging, 34 can affect its normal physiological function.…”

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confidence: 99%

“… 39 As mentioned earlier, ELGs have a robust circadian rhythm as well. 25 , 31 , 32 Accumulated evidence shows sleep disturbance can cause different degrees of damage to the structure and function of ELGs dependent on the time and degree of disturbance. 16 For example, lack of sleep quickly leads to increase of tear film osmotic pressure, shortened tear film breakup time, and decreased tear secretion.…”

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confidence: 99%

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Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Huang

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Sleep loss markedly affects the structure and function of the lacrimal gland and may cause ocular surface disease as a common public health problem. This study aims to investigate the circadian disturbance caused by sleep loss leading to dysfunction of extraorbital lacrimal glands (ELGs). Methods A mouse sleep deprivation (SD) model for sleep loss studies was built in C57BL/6J male mice. After four weeks, the ELGs were collected at three-hour intervals during a 24-hour period. The Jonckheere-Terpstra-Kendall algorithm was used to determine the composition, phase, and rhythmicity of transcriptomic profiles in ELGs. Furthermore, we compared the non-sleep-deprived and SD-treated mouse ELG (i) reactive oxygen species (ROS) by fluorescein staining, (ii) DNA damage by immunostaining for γ-H2Ax, and (iii) circadian migration of immune cells by immunostaining for CD4, CD8, γδ-TCR, CD64, and CX3CR1. Finally, we also evaluated (i) the locomotor activity and core body temperature rhythm of mice and (ii) the mass, cell size, and tear secretion of the ELGs. Results SD dramatically altered the composition and phase-associated functional enrichment of the circadian transcriptome, immune cell trafficking, metabolism, cell differentiation, and neural secretory activities of mouse ELGs. Additionally, SD caused the ROS accumulation and consequent DNA damage in the ELGs, and the ELG dysfunction caused by SD was irreversible. Conclusions SD damages the structure, function, and diurnal oscillations of ELGs. These results highlight comprehensive characterization of insufficient sleep–affected ELG circadian transcriptome that may provide a new therapeutic approach to counteract the effects of SD on ELG function.

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confidence: 99%

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confidence: 99%

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Huang

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Tear fluid samples were collected between 9.00 and 12.00 a. m. to eliminate possible variability caused by diurnal rhythm. [ 9 ] Tears were collected from the lower eyelid for all patients in the same order: with capillary tube (total volume 20 μL, Sigma-Aldrich, Steinheim, Germany) from the left eye [ Figure 1a ], Schirmer strip (Madhu Instruments Pvt. Ltd., New Delhi, India) from the right eye [ Figure 1b ], cellulose microsponge (Sugi ® Eyespear, Kettenbach, Eschenburg, Germany) from the left eye [ Figure 1c ], and flushing with 100 μL saline (Fresenius Kabi, Verona, Italy) from the right eye without an anesthetic [ Figure 1d ].…”

Section: Methodsmentioning

confidence: 99%

Effect of tear fluid sampling and processing on total protein quantity and electrophoretic pattern

Tomečková

Krajčíková

Glinská³

2022

Taiwan Journal of Ophthalmology

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Human tears contain more than 1500 proteins that could be diagnostically relevant. To date, numerous candidates on a biomarker of protein origin were identified for ocular and systemic diseases. However, the suitable sampling method is still the subject of discussion. To address the need for a description of sampling methods properties for possible clinical analyses, we studied a total protein concentration and electrophoretic pattern of tear fluid collected by capillary tubes, Schirmer strips, cellulose microsponges, and flushing. The total protein concentration was 4.339 μg/μL ± 1.905 μg/μL, 0.967 μg/μL ± 0.117 μg/μL, 0.022 μg/μL ± 0.016 μg/μL, and 0.008 μg/μL ± 0.006 μg/μ for the capillary tubes, Schirmer strips, flushing, and cellulose microsponges, respectively. Sodium dodecyl sulfate polyacrylamide electrophoresis showed the different patterns of tear proteins obtained by the above-mentioned sampling methods. These differences could originate from the use of a bigger amount of extraction reagent that was not used in the case of capillary tubes, and retention of the proteins by strips and sponges. Taken together, capillary tubes, Schirmer strips, cellulose microsponges, and flushing represent sensitive and convenient sampling methods for tear fluid collection. For the isolation of proteins from strips and sponges, and for the flushing, less than 100 μL of a reagent should be used to ensure the sufficient concentration of the biomarkers in a trace amount.

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“…Brain and muscle aryl hydrocarbon receptor nuclear translocator‑like protein 1 (Bmal1) and circadian locomotor output cycles kaput (Clock) are the key components of the core molecular clocks [ 12 , 13 ], and they have been found to exist in peripheral tissues, contributing to maintain various physiological homeostatic processes [ 14 ]. The core clock genes are expressed in many ocular tissues, such as retina [ 15 ], lens [ 16 ], lacrimal gland [ 17 ], iris-ciliary body complex [ 18 ], corneal epithelium [ 19 ], and the corneal endothelium [ 20 ]. However, the specific role of core clock genes involved in maintaining ocular health has not been completely clarified.…”

Section: Introductionmentioning

confidence: 99%

Sleep deprivation induces corneal endothelial dysfunction by downregulating Bmal1

Wang,

Dou

et al. 2024

BMC Ophthalmol

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Background Sleep deprivation (SD) is a common public health problem that contributes to various physiological disorders and increases the risk of ocular diseases. However, whether sleep loss can damage corneal endothelial function remains unclear. This study aimed to determine the effect and possible mechanism of SD on the corneal endothelium. Methods Male C57BL/6J mice were subjected to establish SD models. After 10 days, quantitative RT-PCR (qRT-PCR) and western blot or immunostaining for the expression levels of zonula occludens-1 (ZO-1), ATPase Na+/K + transporting subunit alpha 1 (Atp1a1), and core clock genes in the corneal endothelium were evaluated. Reactive oxygen species staining and mitochondrial abundance characterized the mitochondrial function. The regulatory role of Bmal1 was confirmed by specifically knocking down or overexpressing basic helix-loop-helix ARNT like 1 protein (Bmal1) in vivo. In vitro, a mitochondrial stress test was conducted on cultured human corneal endothelial cells upon Bmal1 knockdown. Results SD damaged the barrier and pump functions of mouse corneal endothelium, accompanied by mitochondrial dysfunction. Interestingly, SD dramatically downregulated the core clock gene Bmal1 expression level. Bmal1 knockdown disrupted corneal endothelial function, while overexpression of Bmal1 ameliorated the dysfunction induced by SD. Mitochondrial bioenergetic deficiency mediated by Bmal1 was an underlying mechanism for SD induced corneal endothelial dysfunction. Conclusion The downregulation of Bmal1 expression caused by SD led to corneal endothelial dysfunction via impairing mitochondrial bioenergetics. Our findings offered insight into how SD impairs the physiological function of the corneal endothelium and expanded the understanding of sleep loss leading to ocular diseases.

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Circadian clock regulates tear secretion in the lacrimal gland

Cited by 9 publications

References 33 publications

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Sleep Loss Causes Dysfunction in Murine Extraorbital Lacrimal Glands

Effect of tear fluid sampling and processing on total protein quantity and electrophoretic pattern

Sleep deprivation induces corneal endothelial dysfunction by downregulating Bmal1

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