Thrombospondin-derived peptide attenuates Sjögren's syndrome-associated ocular surface inflammation in mice

Purpose To present a new indicator that measures the sulci of the lacrimal lake of the eye according to the degrees of ocular abduction at which they vanish. This new approach will help determine the severity and progression of mucosal retraction in ocular surface diseases. Methods A total of 181 eyes of 94 healthy persons, 130 eyes of 65 patients with Sjögren's syndrome, and 30 eyes of 15 patients with ocular pemphigoid were examined using the slit lamp. We recorded the vanishing point of the three main lacunar sulci (plico-bulbar, plico-caruncular and dermo-caruncular) while abducting. Results In healthy persons, the average vanishing points for the first and second lacunar sulci were respectively, 53.2° ± 12.3 and 54.5° ± 9.8. In patients with Sjögren's syndrome, 49.53° ± 10.81 and 53.17° ± 7.28 and in patients with incipient ocular cicatricial pemphigoid, 42.69° ± 14.33 and 44.46° ± 16.85. Statistical significance was p < 0.005. Conclusions The lacunar sulci are shallower and vanish sooner in ocular cicatricial pemphigoid and Sjögren syndrome than in normals. Investigating the vanishing point of the lacunar sulci while abducting is useful for grading the shrinkage of the conjunctiva, caruncle and medial canthus.

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Sjögren’s Syndrome-Like Ocular Surface Disease in Thrombospondin-1 Deficient Mice

American Journal Of Pathology ◽

10.2353/ajpath.2009.081058 ◽

2009 ◽

Vol 175 (3) ◽

pp. 1136-1147 ◽

Cited By ~ 74

Author(s):

Bruce Turpie ◽

Takeru Yoshimura ◽

Abha Gulati ◽

Jose David Rios ◽

Darlene A. Dartt ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Ocular Surface Disease ◽

Thrombospondin 1 ◽

Deficient Mice ◽

Sjögren‘S Syndrome

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Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

Mediators of Inflammation ◽

10.1155/2013/636812 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 44

Author(s):

L. Contreras-Ruiz ◽

A. Ghosh-Mitra ◽

M. A. Shatos ◽

D. A. Dartt ◽

S. Masli

Keyword(s):

Sjögren’S Syndrome ◽

Inflammatory Cytokines ◽

Goblet Cell ◽

Ocular Surface ◽

Cell Function ◽

Sjögren's Syndrome ◽

Goblet Cells ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Sjögren‘S Syndrome

Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-αand IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

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Ocular Surface Disease in Sjögren's Syndrome: Management in a Scleral Lens Clinical Practice

Journal of Contact lens Research and Science ◽

10.22374/jclrs.v4i1.36 ◽

2020 ◽

Vol 4 (1) ◽

pp. e12-e22

Author(s):

Daddi Fadel ◽

Melissa Barnett

Keyword(s):

Quality Of Life ◽

Sjögren’S Syndrome ◽

Dry Eye ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Autologous Serum ◽

Sjögren‘S Syndrome

Sjögren’s syndrome is a chronic, autoimmune, systemic disease characterized by lymphocytic infiltration and malfunction of the exocrine glands, primarily the lacrimal and salivary glands, resulting in predominant symptoms of dry eye and dry mouth. Sjögren’s syndrome is a highly prevalent condition and is one of the most common systemic, rheumatic, autoimmune diseases, affecting up to 1.4% of adults in the United States, second only to rheumatoid arthritis in its prevalence in North America. Primary Sjögren’s syndrome has shown to affect patients’ health-related quality-of-life due to dryness, chronic pain, depression, anxiety,physical and mental fatigue, and neuropsychiatric symptoms. Scleral lenses (SLs) have shown to be significantly beneficial in relieving symptoms and improvingquality-of-life in patients with Sjögren’s syndrome and dry eye disease. SLs may be used concurrently with the other therapies including ocular lubricants, eyelid hygiene, punctal occlusion, topical prescription medications, and autologous serum. This manuscript reviews the implication of Sjögren’s syndrome on the ocular surface and quality-of-life and describes how SLs, in combination with other treatments, may be beneficial.

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Degradation of proteoglycan 4/lubricin by cathepsin S: Potential mechanism for diminished ocular surface lubrication in Sjögren's syndrome

Experimental Eye Research ◽

10.1016/j.exer.2017.05.006 ◽

2017 ◽

Vol 161 ◽

pp. 1-9 ◽

Cited By ~ 17

Author(s):

Suresh C. Regmi ◽

Michael L. Samsom ◽

Miriam L. Heynen ◽

Gregory D. Jay ◽

Benjamin D. Sullivan ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Cathepsin S ◽

Potential Mechanism ◽

Proteoglycan 4 ◽

Sjögren‘S Syndrome

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Bacterial Distribution On The Ocular Surface of Patients With Primary Sjögren’s Syndrome

10.21203/rs.3.rs-522331/v1 ◽

2021 ◽

Author(s):

Yong Chan Kim ◽

Bak Noon Ham ◽

Kui Dong Kang ◽

Jun Myeong Yun ◽

Man Jae Kwon ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Dry Eye ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Rrna Genes ◽

Group A ◽

Group B ◽

Sjögren‘S Syndrome

Abstract Many studies have shown that gut microbial dysbiosis is a major factor in the etiology of autoimmune diseases but none have suggested that the ocular surface (OS) microbiome is associated with Sjögren’s syndrome (SS). In this prospective study, we analyzed bacterial distribution on the OS in patients with primary SS. Among the 120 subjects included in this study, 48 patients (group A) had primary SS, whereas 72 subjects (group B) had dry eye symptoms that were unrelated to SS. We evaluated clinical dry eye parameters such as the OS disease index, ocular staining score, Schirmer’s test, and tear break-up time. Conjunctival swabs were used to analyze the microbial communities from the two groups. Bacterial 16S rRNA genes were sequenced using the Illumina MiSeq platform, and the data were analyzed using the QIIME 1.9.1 program. The Shannon index was significantly lower in group A than in group B microbiota. An analysis of similarity using the Bray–Curtis distance method found no difference in beta-diversity between the two groups. In group A, Actinobacteria at the phylum level and Corynebacteria at the genus level exhibited low abundance, but the differences were not statistically significant. SS apparently decreases the diversity of the OS microbial community and may affect the abundance of some bacterial strains at the phylum and genus levels. These observations may be important for the pathophysiology of SS and should be investigated in future studies.

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Thrombospondin-1 Is Necessary for the Development and Repair of Corneal Nerves

International Journal of Molecular Sciences ◽

10.3390/ijms19103191 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3191 ◽

Cited By ~ 5

Author(s):

Yukako Tatematsu ◽

Qalbi Khan ◽

Tomas Blanco ◽

Jeffrey Bair ◽

Robin Hodges ◽

...

Keyword(s):

Confocal Microscopy ◽

Sjögren’S Syndrome ◽

Dry Eye ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Corneal Nerves ◽

Thrombospondin 1 ◽

Sjögren‘S Syndrome

Thrombospondin-1-deficient (TSP-1−/−) mice are used as an animal model of Sjögren’s Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sjögren’s Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1−/− and wild type (WT) mice. The structure and subtype of nerves were characterized by immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. Cytokine expression analysis was determined by Q-PCR and the number of monocytes was measured by immunohistochemistry. We found that only the pro-inflammatory cytokine MIP-2 increased in young corneas of TSP-1−/− compared to WT mice, but tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1−/− mouse corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P (SubP)-containing corneal nerves decreased in older, but not younger TSP-1−/− compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory nerves exhibit distinct structural deficiencies as disease progresses in TSP-1−/− mice, suggesting that: (1) TSP-1 is needed for the development or repair of these nerves and (2) impaired afferent corneal nerve structure and hence function may contribute to ocular surface dysfunction that develops as TSP-1−/− mice age.

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Assessment of mucin-related gene alterations following treatment with rebamipide ophthalmic suspension in Sjögren’s syndrome-associated dry eyes

PLoS ONE ◽

10.1371/journal.pone.0242617 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242617

Author(s):

Jun Shoji ◽

Noriko Inada ◽

Akiko Tomioka ◽

Satoru Yamagami

Keyword(s):

Sjögren’S Syndrome ◽

Ocular Surface ◽

Sjögren's Syndrome ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Mrna Levels ◽

Impression Cytology ◽

Dry Eyes ◽

Ophthalmic Suspension ◽

Sjögren‘S Syndrome

Ocular surface mucins are thought to play vital roles in maintaining the homeostasis of the pre-ocular surface tear film. We performed ocular surface tests with impression cytology to assess the expression levels of mucin-related genes on the ocular surface in healthy eyes. In addition, we investigated alterations in mucin-related gene expression secondary to treatment with rebamipide ophthalmic suspension in patients with Sjögren’s syndrome-associated dry eyes (SS-DE). Thirty-three healthy individuals (control group) and 13 patients from our hospital with SS-DE were enrolled. Impression cytology was performed using Schirmer’s test paper for RNA sampling. The mRNA levels of SAM-pointed domain-containing ETS-like factor (SPDEF), mucin 5AC (MUC5AC), and mucin 16 (MUC16) were determined using a real-time reverse transcription-polymerase chain reaction. The ocular surface test was performed once for the control group, and at baseline as well as 2, 4, 8, and 12 weeks after treatment in the Sjögren’s syndrome-associated dry eyes group. mRNA levels of SPDEF, MUC5AC, and MUC16 were not significantly different between the control and SS-DE groups before rebamipide ophthalmic suspension treatment. SPDEF mRNA levels in control subjects were significantly correlated with levels of MUC5AC. Among SS-DE patients, SPDEF mRNA levels were significantly increased at 2, 4, and 8 weeks after treatment compared with baseline levels. MUC16 mRNA levels were significantly decreased from baseline levels at 4 and 8 weeks post-treatment. Ocular surface test using impression cytology is a clinically useful tool for assessing mucous conditions on the ocular surface and can be used to determine the effects of instillation treatment with eye drops that affect mucin production at the ocular surface.

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