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Journal Francais D'ophtalmologie Oct 2022In parallel to ocular surface disease in dry eye there is often a dysfunctionality of the lacrimal gland apparatus. The functionality of the lacrimal gland is of major...
INTRODUCTION
In parallel to ocular surface disease in dry eye there is often a dysfunctionality of the lacrimal gland apparatus. The functionality of the lacrimal gland is of major importance for maintenance of ocular surface integrity and health, even in conditions of enhanced stimulation and secretion requirements. Such enhanced secretion demands can push the lacrimal gland to its limits, with maximized tear fluid secretion and increased flow through the lacrimal ducts. The goal of this study was to investigate whether G protein-coupled receptor GPR-68 is present in the lacrimal gland, as this protein has recently been shown to be sensitive to flow rate and osmolarity.
METHODS
For this purpose, de-identified sections of human lacrimal gland tissue were stained for the presence of G protein-coupled receptor 68 with specific antibodies using immunohistochemistry.
RESULTS
Specific staining was detected in the acini and ducts of human lacrimal gland. In the ducts, the specific staining was found around the lumen of the ducts. In the acini, the specific staining was observed more towards the lumen but also intercellularly between the acinar cells.
DISCUSSION
The detection of G protein-coupled receptor GPR-68 in the lacrimal gland, especially around the lumen of the ducts, raises the question about its function and purpose. Activation of GPR68 leads to modification of various cell functions and is associated with regulation of inflammation. Accordingly, enhanced, secretion-induced, augmentation of flow might exert fluid flow stress on the ducts and acini. This might lead to transient, localized activation of GPR-68 and secondary inflammation within the gland. Depending on the intensity, continuity or repetitive nature of the stimuli, exhaustion of the lacrimal gland secretion capacity might follow, and chronicity of the inflammation in the parenchyma as well as around the ducts might be a consequence.
CONCLUSION
G protein-coupled receptor GPR-68, sensitive to flow, is present in the human lacrimal gland. Increased flow, triggered by sensations such as are typical for dry eye, might lead to local inflammation. It is possible that these sensations might serve as a better indicator for the need and success of therapy than the clinical signs of dry eye disease, at least in the early stages of the disease.
Topics: Dry Eye Syndromes; Humans; Immunohistochemistry; Inflammation; Lacrimal Apparatus; Receptors, G-Protein-Coupled; Tears
PubMed: 35623913
DOI: 10.1016/j.jfo.2022.02.009 -
The American Journal of Pathology Dec 2020The lacrimal gland is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tears in mammals. Many systemic diseases...
The lacrimal gland is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tears in mammals. Many systemic diseases such as Sjögren syndrome, rheumatoid arthritis, and diabetes can alter the lacrimal gland function, eventually resulting in aqueous tear-deficient dry eye. Here, a high-fat diet (HFD) experimental mouse model was used to clarify how hyperlipidemia affects lacrimal gland function. Aqueous tear secretion fell about 50% after 1 month on a HFD. Lipid droplets accumulated in the matrix and acinar cells of the lacrimal gland after this period, along with changes in the lipid metabolism, changes in gene expression levels, and disruption of fatty acid oxidative activity. Immune cell infiltration and rises in the gene expression levels of the inflammation-related cytokines Il1β, Tnfα, Tsg6, Il10, Mmp2, and Mmp9 were found. HFD also induced mitochondrial hypermegasoma, increased apoptosis, and decreased lacrimal gland acinar cell proliferation. Replacement of the HFD with the standard diet partially reversed pathologic changes in the lacrimal gland. Similarly, supplementing the HFD with fenofibrate also partially reversed the inhibited tear secretion and reduced lipid accumulation, inflammation, and oxidative stress levels. The authors conclude that a HFD induces pathophysiological changes and functional decompensation of the lacrimal gland. Therefore, ingestion of a HFD may be a causative factor of dry eye disease.
Topics: Animals; Cytokines; Diet, High-Fat; Disease Models, Animal; Dry Eye Syndromes; Lacrimal Apparatus; Male; Mice, Inbred C57BL; Mitochondria; Sjogren's Syndrome; Tears
PubMed: 32919976
DOI: 10.1016/j.ajpath.2020.09.002 -
Acta Ophthalmologica Scandinavica May 2007The role of radiotherapy in ophthalmic practice continues to grow. This growth has seen an expansion of indications for radiotherapy, a refinement of the modalities that... (Review)
Review
The role of radiotherapy in ophthalmic practice continues to grow. This growth has seen an expansion of indications for radiotherapy, a refinement of the modalities that can be used and a reduction in the ocular and adnexal complications that result from this form of therapy. The compendium of indications for radiotherapy in ophthalmology continues to grow and now includes many conditions such as the treatment of lid and adnexal disease, ocular surface disorders and both benign and malignant disease of the posterior segment and optic pathways. The radiotherapeutic modalities employed to manage these conditions are numerous and include both radioactive plaques (brachytherapy) and external beam radiation techniques. New techniques such as stereotactic radiosurgery are delivering benefits in the management of conditions such as optic nerve sheath meningioma, where the treatment of this blinding and occasionally life-threatening intracranial neoplasm now results in fewer adverse affects. The purpose of this review is to give a brief overview of the indications and treatment modalities, and a more in-depth discussion of the potential side-effects when radiotherapy is used for ocular and periorbital disease.
Topics: Eye Diseases; Humans; Lacrimal Apparatus Diseases; Neoplasms, Radiation-Induced; Osteoradionecrosis; Radiation Injuries; Radiodermatitis; Radiotherapy
PubMed: 17488452
DOI: 10.1111/j.1600-0420.2006.00822.x -
Nihon Rinsho Men'eki Gakkai Kaishi =... Feb 2008Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both... (Review)
Review
Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both diseases are characterized with elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the glands. Clinical analyses were performed in 40 patients with systemic IgG4-related plasmacytic syndrome (SIPS) who consulted the doctors in Sapporo Medical University Hospital. Our patients were mainly middle-aged or elderly females. The average age was 58.9 years. The diagnosis was following ; 33 cases with Mikulicz's disease, 3 cases with Küttner's tumor, and 4 cases with IgG4-related dacryoadenitis. Slight dysfunction of lacrimal and salivary gland was observed in about 60% of them. Antinuclear antibodies were detected in only 15% of the cases with SIPS. Almost all, except one case, did not have anti-SS-A or anti-SS-B antibodies. Interestingly, hypocomplementemia was revealed in 30% of them. The complications of SIPS include autoimmune pancreatitis, tubulointerstitial nephritis, retroperitoneal fibrosis, prostatitis, and so on. SIPS is mainly treated by the administration of steroids. We started to prescribe much quantity of prednisolone to the patients with organ failure. The recurrence was admitted in the 3 patients for the followed 16 years. We present here the problems and prospects in SIPS.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunoglobulin G; Male; Middle Aged; Mikulicz' Disease; Plasma Cells; Sjogren's Syndrome; Syndrome
PubMed: 18311037
DOI: 10.2177/jsci.31.1 -
Frontiers in Cell and Developmental... 2022Oxidative stress (OS) is a major disruption in the physiology of the lacrimal functional unit (LFU). Antioxidant enzymes have dual protective activities: antioxidant and... (Review)
Review
Oxidative stress (OS) is a major disruption in the physiology of the lacrimal functional unit (LFU). Antioxidant enzymes have dual protective activities: antioxidant and antimicrobial activities. Peroxidases have been indistinctly used as markers of the secretory activity of the LFU and implicated in the pathophysiology, diagnosis and treatment of dry eye disease (DED), even though they comprise a large family of enzymes that includes lactoperoxidase (LPO) and glutathione peroxidase (GPO), among others. Assays to measure and correlate OS with other local LFU phenomena have methodological limitations. Studies implicate molecules and reactions involved in OS as markers of homeostasis, and other studies identify them as part of the physiopathology of diseases. Despite these conflicting concepts and observations, it is clear that OS is influential in the development of DED. Moreover, many antioxidant strategies have been proposed for its treatment, including calorie restriction to nutritional supplementation. This review offers a critical analysis of the biological mechanisms, diagnostic outcomes, drug use, dietary supplements, and life habits that implicate the influence of OS on DED.
PubMed: 35359431
DOI: 10.3389/fcell.2022.824726 -
Eye & Contact Lens Mar 2020The glycocalyx is a dense and diverse coat of glycans and glycoconjugates responsible for maintaining cell surface integrity and regulating the interaction of cells with... (Review)
Review
The glycocalyx is a dense and diverse coat of glycans and glycoconjugates responsible for maintaining cell surface integrity and regulating the interaction of cells with the external environment. Transmembrane mucins such as MUC1 and MUC16 comprise a major component of the epithelial glycocalyx and are currently used to monitor disease progression in cancer. At the ocular surface, multiple lines of evidence indicate that abnormal expression of the enzymes responsible for glycan biosynthesis during pathological conditions impairs the glycosylation of transmembrane mucins. It is now becoming clear that these changes contribute to modify the interaction of mucins with galectin-3, a multimeric lectin crucial for preserving the ocular surface epithelial barrier. This review highlights the potential of using the epithelial glycocalyx as a reliable source for the generation of biomarkers to diagnose and monitor ocular surface disease.
Topics: Biomarkers; Conjunctiva; Epithelium, Corneal; Eye Diseases; Glycocalyx; Humans; Lacrimal Apparatus; Tears
PubMed: 31469755
DOI: 10.1097/ICL.0000000000000653 -
International Journal of Molecular... Jan 2023Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye...
Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model.
Topics: Female; Animals; Mice; Sjogren's Syndrome; Tears; Mice, Inbred NOD; Dry Eye Syndromes; Lacrimal Apparatus; Mesenchymal Stem Cells; Biomarkers; Cytokines; Disease Models, Animal
PubMed: 36674547
DOI: 10.3390/ijms24021039 -
Frontiers in Immunology 2022Conjunctival intraepithelial lymphocytes, tear soluble molecules and commensal microbiota have important roles in the ocular mucosal immune response in healthy and...
Conjunctival intraepithelial lymphocytes, tear soluble molecules and commensal microbiota have important roles in the ocular mucosal immune response in healthy and diseased subjects. For the purpose of this study, the cellular and microbial populations of the conjunctiva and the lacrimal soluble molecules were analyzed to find the main biomarkers in allergic conjunctivitis. A total of 35 healthy subjects, 28 subjects with seasonal allergic conjunctivitis and 32 subjects with perennial allergic conjunctivitis were recruited to obtain peripheral blood, conjunctival brush cytology, tear fluid and microbiota samples. Flow cytometry for lymphocytes, multiplex bead assays for cytokines and high-throughput DNA sequencing for microbiome analysis were used. For perennial allergic conjunctivitis, an increased proportion of Th2 and NKT lymphocytes was found, while CD3+TCRγδ+ lymphocytes and double negative MAIT cells were decreased. In contrast, seasonal allergic conjunctivitis was distinguished by an increase in Th17 and Th22 cell proportions, while the Th1 cell proportion decreased. Among tear fluid, the vast majority of pro-inflammatory cytokines (especially Th2 and Th17 cytokines) in perennial allergies and MMP-9 together with IgA in seasonal allergies were increased. In contrast, TGF-β2 was decreased in both forms of conjunctivitis. Finally, fungal ( species) and bacterial ( and species) colonization were observed in the perennial allergic conjunctivitis group. These results provide the basis for the development of a disease profile for perennial allergic conjunctivitis and open the door to new therapeutic and diagnostic strategies.
Topics: Chronic Disease; Conjunctiva; Conjunctivitis, Allergic; Cytokines; Humans; Intraepithelial Lymphocytes; Microbiota
PubMed: 35935953
DOI: 10.3389/fimmu.2022.911022 -
International Journal of Molecular... Feb 2023Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune...
Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased compared to healthy mice and Thrombospondin-1-null (TSP-1) compared to TSP-1 mice. Inflammasome activation was investigated by immunostaining using the reporter mouse, by Western blotting, and by RNAseq. LPS/Nigericin, IL-1α and chronic inflammation induced inflammasomes in lacrimal gland epithelial cells. Acute and chronic inflammation of the lacrimal gland upregulated multiple inflammasome sensors, caspases 1/4, and interleukins and . We also found increased IL-1β maturation in Sjögren's syndrome models compared with healthy control lacrimal glands. Using RNA-seq data of regenerating lacrimal glands, we found that lipogenic genes were upregulated during the resolution of inflammation following acute injury. In chronically inflamed lacrimal glands, an altered lipid metabolism was associated with disease progression: genes for cholesterol metabolism were upregulated, while genes involved in mitochondrial metabolism and fatty acid synthesis were downregulated, including peroxisome proliferator-activated receptor alpha (PPARα)/sterol regulatory element-binding 1 (SREBP-1)-dependent signaling. We conclude that epithelial cells can promote immune responses by forming inflammasomes, and that sustained inflammasome activation, together with an altered lipid metabolism, are key players of Sjögren's syndrome-like pathogenesis in the mouse lacrimal gland by promoting epithelial dysfunction and inflammation.
Topics: Animals; Mice; Lacrimal Apparatus; Sjogren's Syndrome; Inflammasomes; Thrombospondin 1; Lipid Metabolism; Lipopolysaccharides; Nigericin; Mice, Inbred NOD; Mice, Inbred C57BL; Inflammation; Epithelial Cells; Immunity
PubMed: 36901740
DOI: 10.3390/ijms24054309 -
Eye (London, England) Feb 2021To describe patients with sarcoid-like granulomatous orbitopathy (SLGO), the rate of known and subsequent systemic sarcoidosis, and the treatment and outcome for the...
AIM
To describe patients with sarcoid-like granulomatous orbitopathy (SLGO), the rate of known and subsequent systemic sarcoidosis, and the treatment and outcome for the condition.
PATIENTS AND METHODS
Retrospective review of patients with SLGO presenting between 1990 and 2018, excluding solely lid or lacrimal drainage disease.
RESULTS
Sixty-one patients (45 female; 74%) were identified, 54 having biopsy-proven sarcoidosis (47 orbital, 24 prior extra-orbital), and half were Afro-Caribbean. The average age at presentation was 45.3 years (range 18-78 years), with the commonest symptoms being swelling, pain and diplopia; of clinical signs, most patients (87%) had eyelid swelling, reduced motility (25%), and disease-related visual impairment (10%). Localized dacryoadenitis was present in 49/61 (21/49 bilateral) patients, and more diffuse disease in 28/61 (8/28 bilateral). Systemic involvement was found in 23 (62%) of the 37 first presenting with orbital disease. Twenty-three (38%) patients were observed and two-thirds received oral corticosteroids, with 53/61 (87%) patients having subjective and objective clinical improvement. The average follow-up was 53.4 months (range 1-315 months) and clinical recurrence occurred in 12 (20%) patients at 26.5 months (range 1-115 months) after first diagnosis.
CONCLUSIONS
Systemic sarcoidosis may be discovered in about two-thirds of patients presenting with SLGO (that tends to present with inflammatory features), but the treatment response appears similar in patients with known sarcoidosis and those with newly-diagnosed systemic disease after orbital presentation. With long-term follow-up, a third of patients have spontaneous regression of orbital disease, but 20% have recurrence after reducing or stopping systemic immunosuppression.
Topics: Adolescent; Adult; Aged; Female; Graves Ophthalmopathy; Humans; Lacrimal Apparatus Diseases; Middle Aged; Orbital Diseases; Retrospective Studies; Sarcoidosis; Young Adult
PubMed: 32317795
DOI: 10.1038/s41433-020-0874-4