Tackling Chronic Uveitis: Lessons from the Clinic and the Lab

Soumyava BasuIndia Speaker Chronic uveitis: lessons from the clinic and the labChronic, recurrent inflammation is the primary cause of vision loss and structural complications (photoreceptor loss, cataract, glaucoma, and others) in uveitis. To understand if local factors drive chronic inflammation, we investigated the clinical patterns of recurrent inflammation, and the immunological landscape of vitreous samples, in non-infectious uveitis. In the clinical studies, we retrospectively analyzed HLA-B27 acute anterior uveitis (AAU) patients with documented 2 recurrences for the laterality patterns of recurrent inflammation. Recurrence patterns were classified as ipsilateral (group A) and contralateral (group B) based on the laterality of the second episode. We found that ipsilateral recurrences are more common and severe in HLA-B27 AAU, regardless of the presence of systemic disease or therapy. Similar results were also noted for recurrent inflammation in Behcet’s uveitis, supporting the hypothesis that an eye-specific immune memory exists in non-infectious uveitis. To further characterize the eye-specific immune-memory, we investigated the immune phenotypes and functional attributes of eye-infiltrating immune cells in the vitreous fluids of uveitis patients. Among the various memory T-cell populations in the vitreous, we found CD69+CD103+ tissue resident memory (TRM) T-cell populations. Although the primary function of these cells is long-term immune protection, these TRM cells have also been linked to chronic and recurrent inflammation in numerous autoimmune diseases affecting various organs. Our studies revealed that eye-infiltrating CD4 and CD8 TRMs are functionally distinct, antigen-responsive, and associated with disease prognosis in uveitis, underscoring their potential as biomarkers and possible therapeutic targets.