Abstract
Purpose :
Sjögren‘s syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lacrimal gland (LG) and salivary gland (SG) injury. This study aims to establish a mouse model that can accurately simulate the pathological process of SS, characterized by early involvement of the eye symptom.
Methods :
The C57/B6J mice were divided into four groups: PBS induction (PBS-in), SG protein induction (SG-in), LG protein induction (LG-in), and LG and SG protein mixture induction (MIX-in). The proteins were mixed with complete Freund's adjuvant, emulsified, and injected subcutaneously into the mice once per week during the first two weeks. From the second week, the mice were immunized every 2 weeks with the protein mixed with incomplete Freund's adjuvant. This immunization was continued until week 24. Corneal changes, tear secretion and salivary secretion were assessed every week. LG and SG samples were subjected to H&E staining, Masson's staining, and immunofluorescence staining to detect the IgG and IgM. The expression of genes such as AQP4, AQP5, and ASMA was analyzed using immunofluorescence and RT-qPCR. Serum levels of antibodies were detected by Elisa.
Results :
At week 3, serum level of antibodies began to rise in each induction group. In the LG-in and MIX-in groups, reduced tear secretion, dryness, and epithelial defects were observed Immune damage to the LG has occurred. At week 4 , the LG exhibited inflammatory cell infiltration primarily composed of B lymphocytes. Fibrosis in the LG started to occur, and the expression of the AQP5 decreased. No changes were observed in the SG. At week 14, the LG showed aggravated inflammatory cell infiltration and fibrosis, with continued impairment of secretion function. The SG experienced immune damage. At week 24, the LG presented significant inflammatory cell infiltration, Fibrosis in the lacrimal gland intensified, and the AQP5 continued to decrease, leading to further impairment of secretion function. The SG exhibited inflammatory cell infiltration. SG fibrosis was evident, with reduced expression of the AQP5 and impaired secretion function.
Conclusions :
This induction mouse model of SS can simulate changes in serum, LG and SG pathology, enabling the evaluation of early, progressive, and late features of SS. It can provide a research foundation for identifying specific autoantibodies targeting the LG and early diagnosis and treatment targets for SS.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.