Relationships between activated dendritic cells and dry eye symptoms and signs

Levine, Harry; Hwang, Jodi; Dermer, Harrison; Mehra, Divy; Feuer, William J.; Galor, Anat

doi:10.1016/j.jtos.2021.06.001

Cited by 32 publications

(33 citation statements)

References 65 publications

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“…These changes include an increase in the quantity, change in location (migration from the periphery to the center of the cornea), and an increase in the expression of surface markers (MHC-II, CD86, etc.). 50 , 51 Through in vivo experiments, we proved that after topical application of recombinant NTN-1, the number of corneal DCs and the frequency of CD11c + CD86 + DCs decreased significantly, confirming the inhibitory effect of NTN-1 on DC activation.…”

Section: Discussionmentioning

confidence: 68%

Corneal Epithelium–Derived Netrin-1 Alleviates Dry Eye Disease via Regulating Dendritic Cell Activation

Chen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To investigate the expression of corneal epithelium–derived netrin-1 (NTN-1) and its immunoregulatory function in dry eye disease (DED) using a DED mouse model. Methods We generated DED mouse models with desiccating stress under scopolamine treatment. RNA sequencing was performed to identify differentially expressed genes (DEGs) in the corneal epithelium of DED mice. NTN-1 expression was analyzed via real-time PCR, immunofluorescence staining, and immunoblotting. The DED mice were then treated with recombinant NTN-1 or neutralizing antibodies to investigate the severity of the disease, dendritic cell (DC) activation, and inflammatory cytokine expression. Results A total of 347 DEGs (292 upregulated and 55 downregulated) were identified in the corneal epithelium of DED mice: corneal epithelium–derived NTN-1 expression was significantly decreased in DED mice compared to that in control mice. Topical recombinant NTN-1 application alleviated the severity of the disease, accompanied by restoration of tear secretion and goblet cell density. In addition, NTN-1 decreased the number of DCs, inhibited the activation of the DCs and Th17 cells, and reduced the expression of inflammatory factors in DED mice. In contrast, blocking endogenous NTN-1 activity with an anti–NTN-1 antibody aggravated the disease, enhanced DC activation, and upregulated the inflammatory factors in the conjunctivae of DED mice. Conclusions We identified decreased NTN-1 expression in the corneal epithelium of DED mice. Our findings elucidate the role of NTN-1 in alleviating DED and impeding DC activation, thereby indicating its therapeutic potential in suppressing ocular inflammation in DED.

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Section: Discussionmentioning

confidence: 68%

Corneal Epithelium–Derived Netrin-1 Alleviates Dry Eye Disease via Regulating Dendritic Cell Activation

Chen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Consistent with epithelial ICs being more populous in the peripheral cornea, seven such images were found to be required to achieve the same level of precision in this region. In the absence of evidence to inform optimal image sampling methods, prior clinical studies have used a wide variety of image sample sizes, ranging from three ( 9 , 15 , 19 – 22 ) to twelve ( 24 ) non-overlapping images. The analyses in the current study indicate that central corneal epithelial IC density estimates derived from eight randomly sampled images only reach the above accepted level of precision 80% of the time; with the use of five randomly selected images, the IC density estimates are predicted to only achieve the precision level of not being more than 50% different from the true mean, 80% of the time.…”

Section: Discussionmentioning

confidence: 99%

“…In terms of image selection methods, a frequent approach involves an observer manually identifying a designated number of “representative images” for analysis; the use of three such images is common ( 9 , 15 , 19 – 22 ). However, observer bias might be expected to affect the validity of corneal epithelial IC density estimates derived from a small, subjectively curated image set ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous corneal IVCM studies have used a variety of sample sizes, including quantifications from three ( 9 , 15 , 19 – 22 ), five ( 6 ), eight ( 23 ), or twelve ( 24 ) non-overlapping images, to derive an estimate of central corneal epithelial IC density for a single participant. Using a larger sample would be expected to yield a more accurate estimate, as a larger portion of the corneal region is directly quantified; the trade-off is that more time and effort is required for the image acquisition, selection and analysis ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

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Defining an Optimal Sample Size for Corneal Epithelial Immune Cell Analysis Using in vivo Confocal Microscopy Images

Zhang

Chinnery

et al. 2022

Front. Med.

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PurposeIn vivo confocal microscopy (IVCM) images are frequently used to quantify corneal epithelial immune cell (IC) density in clinical studies. There is currently limited evidence to inform the selection of a representative image sample size to yield a reliable IC density estimate, and arbitrary numbers of images are often used. The primary aim of this study was to determine the number of randomly selected, unique IVCM images required to achieve an acceptable level of accuracy when quantifying epithelial IC density, in both the central and peripheral cornea. The secondary aim was to evaluate the consistency and precision of an image selection approach where corneal epithelial IC density was quantified from “three representative images” selected independently by three experienced observers.MethodsAll combinations of two to 15 non-overlapping IVCM images were used for deriving IC density estimates, for both the central and peripheral cornea, in 20 healthy participants; the density value from averaging quantifications in the 16 images was defined as the “true mean”. IC density estimates were compared with the true mean in each corneal region using a mean ratio. Intraclass correlation coefficients (ICCs) were used to evaluate the consistency of the mean ratios of IC density estimates derived from the method involving the manual selection of “three representative images” by the observers. The precision of the IC density estimates was compared to a scenario involving three randomly selected images.ResultsA total of 12 randomly selected, non-overlapping IVCM images were found to be required to produce a corneal epithelial IC density estimate that was within 30% of the true mean, 95% of the time, for the central cornea; seven such images produced an equivalent level of precision in the peripheral cornea. Mean ratios of corneal IC density estimates derived from “three representative images” methods had poor consistency between observers (ICC estimates <0.5) and similar levels of precision when compared with using three randomly selected images (p > 0.05 for all comparisons), in both the central and peripheral cornea.ConclusionsData presented in this study can inform image selection methods, and the sample size required for a preferred level of accuracy, when quantifying IC densities in the central and peripheral corneal epithelium using IVCM images.

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“…A drop of carbomer (Viscotears, CIBA Vision Europe Ltd., Southampton, UK) was served as a lubricant gel both in ocular surface and the disposable sterile polymethylmethacrylate cap (Tomo-Cap; Heidelberg Engineering GmbH, Dossenheim, Germany). Then advanced the cap manually until the gel contacted the central corneal surface as previously dsecribed 14 , 18 . The corneal sub-basal nerves shift centripetally and form a corneal vortex just inferior to the nose of the corneal apex 19 , 20 .…”

Section: Methodsmentioning

confidence: 99%

Alterations in corneal epithelial dendritic cell in Sjogren’s syndrome dry eye and clinical correlations

Hao

Ding

2022

Sci Rep

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We aimed to investigate the density and morphology of corneal dendritic cells (DCs) in dry eye (DE) patients with or without Sjogren’s syndrome (SS). This study included 28 patients with Sjogren’s syndrome dry eye (SSDE), 33 patients with non-Sjogren’s syndrome dry eye (NSSDE), and 30 age and sex matched healthy volunteers. In vivo confocal microscopy (IVCM) was used to investigate density and morphology (size, dendrites, and field) of DC. Compared with NSSDE and healthy group, SSDE showed significantly higher DC density, larger DC size, more DC dendrites with larger DC field (all P < 0.001). Comparison between NSSDE and healthy group demonstrated that DC density, dendrites and field were significantly higher in NSSDE. However, there was no significant difference in DC size (P = 0.076). DC density and morphological parameters showed significant associations with the systemic severity (salivary gland biopsy and serum antibodies) and ocular surface damage. The corneal epithelium DC density and morphological alterations were obvious in SSDE, which reflected higher level of immune activation and inflammatory response in SS. Marked correlations were found between DC density/morphology and systemic/ocular severity. Dynamic assessment of corneal DC may facilitate to clarify pathogenesis, stratify patient, and tailor treatment in SS patients.

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Relationships between activated dendritic cells and dry eye symptoms and signs

Cited by 32 publications

References 65 publications

Corneal Epithelium–Derived Netrin-1 Alleviates Dry Eye Disease via Regulating Dendritic Cell Activation

Corneal Epithelium–Derived Netrin-1 Alleviates Dry Eye Disease via Regulating Dendritic Cell Activation

Defining an Optimal Sample Size for Corneal Epithelial Immune Cell Analysis Using in vivo Confocal Microscopy Images

Alterations in corneal epithelial dendritic cell in Sjogren’s syndrome dry eye and clinical correlations

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