Dysfunction of lacrimal and salivary glands in Sjögren's syndrome: nonimmunologic injury in preinflammatory phase and mouse model.

Sjögren's syndrome (SjS) is a chronic autoimmune disorder characterized by dry eyes and dry mouth due to dacryoadenitis and sialoadenitis with SS-A/Ro and/or SS-B/La autoantibodies in genetically predisposed individuals. Destruction of lacrimal and salivary glands by autoimmune reactions may lead to clinical manifestation. However, the mechanisms behind the decreased volume of secretions in tears and saliva are complex and are not fully understood. Exocrine gland dysfunction may precede autoimmunity (acquired immunity) or represent a process independent from inflammation in the pathogenesis of SjS. The preceded functional and morphologic changes of those tissues by nonimmunologic injury before the development of inflammation at the sites of target organs have been implicated. This paper focuses on the several factors and components relating to glandular dysfunction and morphologic changes by nonimmunologic injury during the preinflammatory phase in mouse model, including the factors which link between innate immunity and adaptive immunity.

Effect of mitomycin C on success rate in dacryocystorhinostomy with silicone tube intubation and improper flaps.

PURPOSE: To assess the effect of mitomycin C on surgical success rate of dacryocystorhinostomy and silicone intubation in patients with improper flaps. METHODS: The study was a randomized clinical trial. The patients with indication for dacryocystorhinostomy surgery with silicone intubation (inappropriate lacrimal sac or nasal mucosal flaps during surgery and/or history of dacryocystitis in the past 3 months) were randomly assigned to application of mitomycin C (0.02%) on surgical flaps (group A) or a control group without mitomycin C application (group B). Main outcome measures were subjective symptomatic improvement and result of irrigation test at last follow-up visit. RESULTS: The study enrolled 88 patients (88 eyes); there were 42 patients in group A and 46 patients in group B. There was an average follow-up of 10 months (range 6-15 months) following surgery. Significant improvement (no tearing with patent lacrimal system in irrigation) was observed in 31 patients (73.8%) in group A and 32 patients (69.6%) in group B. There was no statistically significant difference in no improvement (no change in tearing state and obstruction in irrigation test), relative improvement (decreased tearing and passage of fluid with force in irrigation test), and significant improvement rate between the 2 groups of study (p>0.05). CONCLUSIONS: Application of mitomycin C on surgical flaps during dacryocystorhinostomy surgery with silicone intubation in patients with improper flaps has no proven beneficial effect on success rate of surgery.

Lacrimal gland inflammation is responsible for ocular pathology in TGF-beta 1 null mice.

Mice homozygous for a nonfunctional transforming growth factor-beta 1 gene develop rampant inflammation in vital organs that contributes to a shortened life span. The presence of circulating anti-nuclear anti-bodies, immune deposits in tissues, leukocyte infiltration, and increased major histocompatibility complex antigen expression resembles an autoimmune-like syndrome. One of the overt symptoms that appears in these mice lacking transforming growth factor-beta 1 is the development of dry crusty eyes that close persistently as their health declines. Histologically, the eyes appear normal with little or no inflammation. However, inflammatory lesions, predominantly lymphocytic, develop in the lacrimal glands, disrupting their structure and function and severely limiting their ability to generate tears. This histopathology and aberrant function mimic that of Sjögren's syndrome, a human autoimmune disease characterized by dry eyes and dry mouth. Impeding the leukocyte infiltration into the glands with synthetic fibronectin peptides, which block adhesion, not only prevents the inflammatory pathology but also prevents the persistent eye closure characteristic of these mice.