Unraveling the Pathophysiology of Sjogren Syndrome-Associated Dry Eye Disease

Abstract

Sjogren syndrome (SS) is one of the most common autoimmune diseases. Early clinical manifestations of SS are primarily decreased tear and saliva secretion, leading to dry eye and dry mouth syndromes, but in its later stages, it can become systemic, even resulting in B cell lymphomas. The use of new animal models, coupled with new technologies, is providing exciting insights into the pathogenesis, genetic predisposition, and, possibly, early diagnosis of SS. This article reviews newly described features of SS identified in experimental animal models and their relationship to human disease. New technologies, such as genomics and proteomics, may permit identification of potential candidate genes and biomarkers for disease diagnosis. Current studies using appropriate animal models in parallel with studies of human subjects is rapidly establishing a foundation for new intervention strategies that go beyond merely treating symptoms.

Pathobiology of Sjögren Syndrome: What do we Know?

“…It seems that SS afflicts mostly women (9:1 female to male ratio) in the fourth to fifth decades of life [5]. In the USA, it is estimated that SS affects at least 1.3 million individuals, and that many more are symptomatic but undiagnosed [8]. Symptom prevalence figures in the USA report approximately 5 million individuals suffering from dry eye symptoms, and the prevalence of xerostomia has been calculated to be as high as 75 million [9].…”

“…Several mechanisms have been proposed to describe the ocular involvement in this disorder. Among these, infection (viral), moebian gland dysfunction, and hormonal imbalance are noteworthy [8].…”

“…Its breakdown by caspase 3 produces fragments that may act as tissue-specific antigens. Antibodies against alpha-fodrin have been found in 64 % of patients with SS [1,8,21].…”

“…Antibodies against M3R have the effect of blocking neurogenic reception to acinar cells, either by causing internalization of the receptors or by causing progressive desensitization of these receptors. The constant receptor binding may cause significant reduction in the secretory capacity of glandular acini [8,18].…”

Das Trockene Auge

“…Pathophysiologisch ist eine lymphoplasmazellul ä re Infi ltration der Haupttr ä nendr ü se und der akzessorischen Tr ä nendr ü sen in der Bindehaut mit erh ö hter Expression von proinfl ammatorischen Zytokinen und Bildung von Autoantik ö rpern wie ANAs, Anti-α -fodrin und anti-M3R-Antik ö rpern bedeutsam, die in einem Verlust der exkretorischen Funktion resultiert [15] . Die Pathogenese des SS-assoziierten Trockenen Auges ist komplex.…”