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The Ocular Surface Oct 2023Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates...
PURPOSE
Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland.
METHOD
MECs primary culture was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2 mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control.
RESULT
Treatment with gDNA activated AIM2 inflammasome assembly and function, leading to secretion of interleukin (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2 mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca].
CONCLUSION
Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.
Topics: Female; Mice; Animals; Lacrimal Apparatus; Inflammasomes; Interleukin-18; Mice, Inbred NOD; Inflammation; Genomics
PubMed: 37769964
DOI: 10.1016/j.jtos.2023.09.012 -
Anti-inflammatory & Anti-allergy Agents... 2023The pathogenesis of Sjögren's syndrome involves the activation of NF- κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α,...
BACKGROUND
The pathogenesis of Sjögren's syndrome involves the activation of NF- κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL- 1β, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities.
OBJECTIVE
To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren's syndrome mice model.
METHODS
The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C-), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren's syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 μg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05.
RESULTS
The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group.
CONCLUSION
The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren's syndrome mice model.
Topics: Male; Mice; Animals; Lacrimal Apparatus; Sjogren's Syndrome; Moringa oleifera; Disease Models, Animal; Plant Extracts; Dexamethasone
PubMed: 36305140
DOI: 10.2174/1871523022666221026145110 -
Clinical and Experimental Rheumatology Dec 2022According to a recent survey of patients with the autoimmune disease primary Sjögren's syndrome (pSS), dry eye symptoms are present in 95-98% of pSS patients. As one of... (Review)
Review
According to a recent survey of patients with the autoimmune disease primary Sjögren's syndrome (pSS), dry eye symptoms are present in 95-98% of pSS patients. As one of the most disabling symptoms mentioned by pSS patients, dry eyes have demonstrable effects on quality of their life, leading to eye dryness, itching, and pain, with some patients describing as a recurrent sensation of sand or gravel in the eyes. The symptoms are matched only in prevalence by dry mouth and chronic fatigue. In contrast to the prevalence of dry eye symptoms in pSS and their burden on pSS patients, our comprehension of dry eye disease development is minimal; specifically how function of the tear-fluid producing gland the lacrimal gland (LG), manifests. The comparison becomes stronger again when we consider what we know about dysfunction of the salivary gland (SG) in pSS, for example the appreciation of the transcriptome of 'innately activated' B cells invading the SG, their complicity in formation of lymphoepithelial lesions, and the ability of the SG epithelium to actively contribute to the inflammatory milieu. The exploration of ultrasound imaging as an additional modality to garner information about SG dysfunction in pSS has opened many doors for non-invasive, repeatable imaging in pSS. Here we summarise SG histology and ultrasound phenotype briefly and then juxtapose this with available studies examining LG pathology and ultrasound, and our understanding of LG dysfunction in pSS.
Topics: Humans; Sjogren's Syndrome; Lacrimal Apparatus; Salivary Glands; Dry Eye Syndromes; Ultrasonography
PubMed: 36377565
DOI: 10.55563/clinexprheumatol/z1lzb1 -
The American Journal of Pathology Dec 2021Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the...
Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.
Topics: Aging; Animals; Chronobiology Disorders; Circadian Rhythm; Dysbiosis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S; Transcriptome
PubMed: 34428426
DOI: 10.1016/j.ajpath.2021.08.006 -
Arquivos Brasileiros de Oftalmologia 2021This report is of three cases of sicca syndrome, initially suspected to be Sjögren's syndrome, which was ruled out by clinical and laboratory investigations. The...
This report is of three cases of sicca syndrome, initially suspected to be Sjögren's syndrome, which was ruled out by clinical and laboratory investigations. The patients were a 24-year-old woman, a 32-year-old man, and a 77-year-old woman with chronic symptoms of sicca syndrome, including dry eye syndrome. The first case was associated with the use of isotretinoin, a retinoic acid. The second was associated with the use of anabolic androgenic steroids, and the third was related to a prolactin- secreting pituitary adenoma. All cases manifested sicca, including dry eye syndrome, after those events, and the manifestations persisted. Magnetic resonance imaging revealed bilateral atrophy of the lacrimal gland. The medical history, ocular examinations, laboratory exams, and magnetic resonance images confirmed dry eye syndrome; however, the exams were all negative for Sjögren's syndrome. The lacrimal gland was absent on magnetic resonance imaging in all three cases. The clinical history revealed that the signs and symptoms appeared after chronic exposure to retinoic acid, anabolic androgenic steroids, and a prolactin-secreting pituitary adenoma, respectively. Chronic isotretinoin, anabolic androgenic steroids, and prolactin-secreting pituitary adenoma or, in this last case, its inhibitory treatment, can cause lacrimal gland atrophy, sicca syndrome, and dry eye syndrome, and a differential diagnosis of Sjögren's syndrome. Further studies on doses, time, and other susceptibilities to the long-lasting adverse effects of retinoic acid, anabolic androgenic steroids, and the repercussions of prolactin-secreting pituitary adenoma are necessary to confirm and expand upon these associations.
Topics: Adult; Aged; Androgens; Atrophy; Diagnosis, Differential; Dry Eye Syndromes; Female; Humans; Isotretinoin; Lacrimal Apparatus; Male; Prolactin; Sjogren's Syndrome; Young Adult
PubMed: 33470346
DOI: 10.5935/0004-2749.20210012 -
Eye (London, England) Jan 2023To establish cultures of human lacrimal gland from patient-derived, biopsy-sized, tissue specimens.
OBJECTIVES
To establish cultures of human lacrimal gland from patient-derived, biopsy-sized, tissue specimens.
METHODS
Tissue was obtained after surgical removal from patients without dry eye disease undergoing routine procedures. Samples were subjected to mechanical and enzymatic digestion and resulting cell suspensions were plated onto collagen-coated glass coverslips and grown for up to 21 days. Cultures were analysed by immunocytochemistry and light microscopy, and resultant cellular distributions were compared to those in sections of fixed human lacrimal gland tissue.
RESULTS
Dissociation of biopsy-sized pieces of human lacrimal gland and seeding onto coated surfaces allowed development of a mixed population of cells in vitro. Within 7-14 days, cellular aggregation was observed and by 21 days many cells had organised themselves into distinct three-dimensional complexes. Immunohistochemistry revealed a heterogeneous population of cells, including epithelial, myoepithelial, mesenchymal and progenitor cells. Some of the epithelia labelled positively for lysozyme and lactoferrin.
CONCLUSIONS
Collection and dissociation of biopsy-sized pieces of human lacrimal gland leads to a cellular preparation that can proliferate in vitro and organise into three-dimensional structures. This is the first report detailing that biopsy-collected specimens of human lacrimal gland can be used to establish cell cultures.
Topics: Humans; Lacrimal Apparatus; Cells, Cultured; Epithelial Cells; Immunohistochemistry; Biopsy
PubMed: 35001090
DOI: 10.1038/s41433-021-01872-9 -
Clinical characteristics, radiologic features, and histopathology of biopsied lacrimal gland tumors.Scientific Reports Oct 2023Herein, we described the clinicopathologic and radiologic features of biopsied lacrimal gland tumors. A retrospective case series of 79 patients treated between 2004 and...
Herein, we described the clinicopathologic and radiologic features of biopsied lacrimal gland tumors. A retrospective case series of 79 patients treated between 2004 and 2021 was reviewed. The median age was 48.9 years (range 18.3-88.3 years), with 51.9% females. The histopathologic diagnoses were as follows: immunoglobulin G4-related disease (IgG4-RD) = 23, reactive lymphoid hyperplasia = 14, lymphoma = 14, nonspecific inflammation = 10, adenoid cystic carcinoma (ACC) = 9, and pleomorphic adenoma = 9. The proportion of histopathologic diagnoses did not differ significantly over the range of symptom durations (≤ 1 month, > 1-3 months, > 3 months). Patients with ACC had significantly shorter symptom duration and more frequent proptosis than those with pleomorphic adenoma (p = 0.040 and p = 0.009, respectively). Patients with IgG4-RD were older (median 54.3 years) than those with nonspecific inflammation (36.2 years; p = 0.046). Patients with ACC were more likely to present with diplopia than those with lymphoma (p < 0.001). The superior wedge sign increased the likelihood of ACC compared with that of non-epithelial non-malignant lacrimal gland tumors (relative risk ratio = 13.44, p = 0.002). The overall survival of patients with ACC and lymphoma did not differ significantly. Although these patients present with a short symptom duration, urgent orbital imaging, tissue biopsy, and prompt treatment should be performed in patients with lacrimal gland tumors.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Lacrimal Apparatus; Adenoma, Pleomorphic; Retrospective Studies; Immunoglobulin G4-Related Disease; Lacrimal Apparatus Diseases; Eye Neoplasms; Carcinoma, Adenoid Cystic; Inflammation; Lymphoma; Biopsy
PubMed: 37789105
DOI: 10.1038/s41598-023-43817-0 -
Journal of Ocular Pharmacology and... Oct 2016Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A, A, and A, P2X receptors, and many of the P2Y receptors are... (Review)
Review
PURPOSE
Purinergic receptors play a key role in the function of the lacrimal gland (LG) as P1 purinergic receptors A, A, and A, P2X receptors, and many of the P2Y receptors are expressed.
METHODS
This review examines the current knowledge of purinergic receptors in the LG as well as the signaling pathways activated by these receptors.
RESULTS
These receptors are expressed on the acinar, ductal, and myoepithelial cells. Considerable crosstalk exists between the pathways activated by P2X receptors with those activated by M muscarinic or α adrenergic receptors. The mechanism of the crosstalk between P2X and M muscarinic receptors differs from that of the crosstalk between P2X and α adrenergic receptors.
CONCLUSIONS
Understanding purinergic receptors and how they modulate protein secretion could play a key role in normal and pathological responses of the LG.
Topics: Animals; Humans; Lacrimal Apparatus; Receptors, Adrenergic; Receptors, Cholinergic; Receptors, Purinergic; Signal Transduction
PubMed: 27463365
DOI: 10.1089/jop.2016.0008 -
Acta Ophthalmologica Jun 2013To evaluate the incidence rate, distribution, patient characteristics and indications for surgical intervention of lacrimal gland lesions in Denmark between 1974 and... (Comparative Study)
Comparative Study
PURPOSE
To evaluate the incidence rate, distribution, patient characteristics and indications for surgical intervention of lacrimal gland lesions in Denmark between 1974 and 2007.
MATERIAL AND METHODS
All biopsied/surgically removed lacrimal gland lesions in Denmark during the period 1974-2007 were identified by searching two population-based registries. Specimens were collected and re-evaluated. The following data were collected: age, gender, indications for surgical intervention and local recurrence.
RESULTS
A total of 232 lesions from 210 patients with a histologically verified lesion of the lacrimal gland were included. The incidence rate of lacrimal gland lesions was 1.3/1 000 000/year. The overall annual age- and gender-adjusted incidence rate more than doubled during the study period, owing to an increase in non-malignant lesions. Approximately half of the lesions were neoplasms (119) and 55% (66) of these were malignant. Dacryops constituted 10% (24), inflammatory lesions 27% (62), normal tissue 12% (27), benign tumours 23% (53) and malignant tumours 29% (66). Patients with malignant neoplasms were significantly older than patients with benign neoplasms (63 versus 48 years, p < 0.001). The indication for surgical intervention was suspicion of a tumour in more than 90% of the neoplastic lesions and in 30% of the non-neoplastic lesions.
CONCLUSION
Lacrimal gland lesions that require surgical evaluation are rare in the Danish population and represent a wide spectrum of diagnoses, mostly benign. The overall incidence rate of biopsied lacrimal gland lesions is increasing.
Topics: Adolescent; Adult; Aged; Biopsy; Child; Child, Preschool; Denmark; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Incidence; Infant; Infant, Newborn; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male; Middle Aged; Registries; Retrospective Studies; Young Adult
PubMed: 22471375
DOI: 10.1111/j.1755-3768.2012.02403.x -
Progress in Retinal and Eye Research May 2009The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins. The amount and composition of this... (Review)
Review
The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins. The amount and composition of this layer is critical for the health, maintenance, and protection of the cells of the cornea and conjunctiva (the ocular surface). Small changes in the concentration of tear electrolytes have been correlated with dry eye syndrome. While the mechanisms of secretion of water, electrolytes and proteins from the lacrimal gland differ, all three are under tight neural control. This allows for a rapid response to meet the needs of the cells of the ocular surface in response to environmental conditions. The neural response consists of the activation of the afferent sensory nerves in the cornea and conjunctiva to stimulate efferent parasympathetic and sympathetic nerves that innervate the lacrimal gland. Neurotransmitters are released from the stimulated parasympathetic and sympathetic nerves that cause secretion of water, electrolytes, and proteins from the lacrimal gland and onto the ocular surface. This review focuses on the neural regulation of lacrimal gland secretion under normal and dry eye conditions.
Topics: Animals; Dry Eye Syndromes; Humans; Lacrimal Apparatus; Neurons, Afferent; Neurons, Efferent; Neurotransmitter Agents; Signal Transduction; Tears; Water-Electrolyte Balance
PubMed: 19376264
DOI: 10.1016/j.preteyeres.2009.04.003