B-cell depletion therapy reduces retinal inflammation in experimental autoimmune uveoretinitis

Non-infectious uveitis (NIU) is recognized as a group of autoimmune sight-threatening disorders with complex pathogenesis. This study aims to analyze the pathogenic role of B cells in NIU and evaluate the effectiveness of B cell depletion therapy in experimental autoimmune uveoretinitis (EAU) mice.

We performed high throughput transcriptome sequence on peripheral blood samples from healthy individuals (n = 6) and NIU patients (n = 12), and reanalyzed single-cell RNA transcriptome data of aqueous humor in NIU patients (n = 5). Female C57BL/6 J mice were induced the EAU model through immunization with the IRBP_651-670 peptide. B cell depletion was performed via intravitreal injection of anti-CD20 antibody on day 7 and mice were executed on day 14 following antigen administration. Clinical symptoms were assessed by fundus photography and fundus fluorescein angiography. Pathological sections were analyzed using immunohistochemistry and immunofluorescence. Serum immunoglobulins and inflammatory factors were detected by ELISA.

Transcriptome sequencing and single-cell RNA analysis revealed strong B cell immune responses in both peripheral blood and aqueous humor of NIU patients. Intravitreal injection of anti-CD20 antibody partially reduces B cell numbers, suppresses T cell proliferation in CLNs, and decreases serum IgG and inflammatory cytokines level, which collectively alleviate clinical symptoms and mitigate retinal inflammation. Significant differences in BCR sequences were observed between the NIU groups and healthy controls.

B-cell depletion therapy may offer a novel strategy for the treatment of NIU and identifying specific BCR sequences provides a potential target for both therapeutic intervention and disease monitoring.