Abstract
Presentation Description :
Non-infectious uveitis causes 10% of blindness in the US and disproportionately affects working-aged people, making it a significant cause of vision-related disability. Importantly, uveitis is a heterogeneous group of unique disease entities that are currently defined by clinical features rather than molecular mechanisms. As such the treatment approach is empiric and individual drugs fail 20-50% of patients. Alternatively, more precise molecular characterization of uveitis subtypes should provide pathophysiologic insight with therapeutic potential. Single-cell RNA-Sequencing (scRNA-Seq) facilitates deep, unbiased immune cell profiling of even very small samples, making it ideal for analyzing immune cell infiltrates in the anterior chamber. In this study, we set out to capitalize on the unbiased molecular characterization of individual ocular immune cells afforded by scRNA-Seq to 1) identify pathophysiologic mechanisms with therapeutic potential in uveitis and 2) advance molecular classification of clinical uveitis entities. We found that aqueous immune cell infiltrates differed significantly between patients and correlated with specific clinical phenotypes. Specifically, we found clonally expanded T and B cells, strong evidence of antigen-driven immune responses, in patients with granulomatous uveitis; however, patients with HLA-B27-associated uveitis had aqueous infiltrates dominated by unconventional T cells and myeloid cells.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.