Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Darabad, Raheleh Rahimi; Suzuki, Tomo; Richards, Stephen M.; Zakka, Fouad R.; Barabino, Stefano; Sullivan, David A.

doi:10.1016/j.exer.2014.07.017

Cited by 23 publications

(18 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Table 4 , relatively few genes displaying sex-related differences were expressed by both microarrays. These findings are consistent with our previous investigations, 15 – 17 as well as those of others, 18 – 21 which discovered little agreement between CodeLink and Affymetrix microarrays in the detection of differential gene expression. Although these platforms seem to measure different things, 20 most gene expression changes revealed by each of the platforms are thought to be biologically correct.…”

Section: Resultssupporting

confidence: 93%

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Tellefsen

Morthen

Richards

et al. 2018

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

PurposeSjögren syndrome is an autoimmune disease that occurs primarily in women, and is associated with lacrimal gland inflammation and aqueous-deficient dry eye. We hypothesize that sex-associated differences in lacrimal gland gene expression are very important in promoting lymphocyte accumulation in this tissue and contribute to the onset, progression, and/or severity of the inflammatory disease process. To test our hypothesis, we explored the nature and extent of sex-related differences in gene expression in autoimmune lacrimal glands.MethodsLacrimal glands were collected from age-matched, adult, male and female MRL/MpJ-Tnfrsf6lpr (MRL/lpr) and nonobese diabetic/LtJ (NOD) mice. Glands were processed for the analysis of differentially expressed mRNAs by using CodeLink Bioarrays and Affymetrix GeneChips. Data were evaluated with bioinformatics and statistical software.ResultsOur results show that sex significantly influences the expression of thousands of genes in lacrimal glands of MRL/lpr and NOD mice. The immune nature of this glandular response is very dependent on the Sjögren syndrome model. Lacrimal glands of female, as compared with male, MRL/lpr mice contain a significant increase in the expression of genes related to inflammatory responses, antigen processing, and chemokine pathways. In contrast, it is the lacrimal tissue of NOD males, and not females, that presents with a significantly greater expression of immune-related genes.ConclusionsThese data support our hypothesis that sex-related differences in gene expression contribute to lacrimal gland disease in Sjögren syndrome. Our findings also suggest that factors in the lacrimal gland microenvironment are critically important in mediating these sex-associated immune effects.

show abstract

Section: Resultssupporting

confidence: 93%

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Tellefsen

Morthen

Richards

et al. 2018

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Surprisingly, a recent study using young ArKO mice demonstrated contradictory results, reporting that estrogen deficiency did not lead to a SjS-like inflammation in the lacrimal tissue or to an aqueous-deficient dry eye although estrogen deficiency influenced the expression of sex- and genotype-specific lacrimal gland genes [141]. This study indicates that estrogen deficiency alone may not be sufficient to induce lacrimal pathophysiology especially at a young age.…”

Section: Mouse Modelsmentioning

confidence: 84%

Mouse Models of Primary Sjogren’s Syndrome

Park¹,

Gauna²,

Cha

2015

CPD

View full text Add to dashboard Cite

Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models.

show abstract

“…As we30,33–35 and other investigators36–39 have discovered, the vast majority of lacrimal gland genes in MRL/lpr and NOD female mice, which were identified as differentially expressed by the CL and Affy microarrays, were unique to each platform. Indeed, as demonstrated in Table 4, only 8.5% to 11.1% (T>P), and 7.3% to 16.8% (P>T) of the regulated genes were found by both microarrays.…”

Section: Resultsmentioning

confidence: 75%

Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Morthen

Tellefsen

Richards

et al. 2019

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

PURPOSE. Sjögren syndrome is an autoimmune disorder that occurs almost exclusively in women and is associated with extensive inflammation in lacrimal tissue, an immune-mediated destruction and/or dysfunction of glandular epithelial cells, and a significant decrease in aqueous tear secretion. We discovered that androgens suppress the inflammation in, and enhance the function of, lacrimal glands in female mouse models (e.g., MRL/MpJ-Tnfrsf6 lpr [MRL/lpr]) of Sjögren syndrome. In contrast, others have reported that androgens induce an anomalous immunopathology in lacrimal glands of nonobese diabetic/LtJ (NOD) mice. We tested our hypothesis that these hormone actions reflect unique, strain-and tissue-specific effects, which involve significant changes in the expression of immune-related glandular genes. METHODS. Lacrimal glands were obtained from age-matched, adult, female MRL/lpr and NOD mice after treatment with vehicle or testosterone for up to 3 weeks. Tissues were processed for analysis of differentially expressed mRNAs using CodeLink Bioarrays and Affymetrix GeneChips. Data were analyzed with bioinformatics and statistical software. RESULTS. Testosterone significantly influenced the expression of numerous immune-related genes, ontologies, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in lacrimal glands of MRL/lpr and NOD mice. The nature of this hormone-induced immune response was dependent upon the autoimmune strain, and was not duplicated within lacrimal tissues of nonautoimmune BALB/c mice. The majority of immune-response genes regulated by testosterone were of the inflammatory type. CONCLUSIONS. Our findings support our hypothesis and indicate a major role for the lacrimal gland microenvironment in mediating androgen effects on immune gene expression.

show abstract

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Cited by 23 publications

References 67 publications

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Sex Effects on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Mouse Models of Primary Sjogren’s Syndrome

Testosterone Influence on Gene Expression in Lacrimal Glands of Mouse Models of Sjögren Syndrome

Contact Info

Product

Resources

About