Vitreous transcriptomic profiling reveals miR-4762 as a potential diagnostic biomarker and modulator of disease pathophysiology in Tubercular Uveitis.

UNLABELLED: Tubercular uveitis is an extrapulmonary form of TB characterized by ocular inflammation that clinically mimics other inflammatory eye diseases, including non-tubercular uveitis. Currently, no gold standard test is available for the diagnosis of tubercular uveitis, and it is primarily based on clinical presentation.

OBJECTIVE

To characterise the transcriptional landscape of vitreous fluid of tubercular uveitis and non-tubercular uveitis patients for biomarker identification and gaining insights into disease pathology.

DESIGN

Vitreous fluid samples from uveitis patients were processed for isolation of cells and RNA sequencing to compare the transcriptomic profiles of TB and non-TB uveitis entities. Differentially expressed genes were identified using the criteria of false discovery rate (FDR) < 0.25, fold-change (FC) ≥ 2 or ≤ -2, and p-value <0.05 and the top dysregulated genes were selected for biomarker validation. Additionally, gene set enrichment analysis (GSEA) was performed to explore underlying disease mechanisms.

RESULTS

RNA sequencing revealed distinct vitreous fluid gene expression patterns in TB uveitis and non-TB uveitis. Notably, MIR581 and MIR4762, encoding miR-581 and miR-4762, respectively, were among the most upregulated genes. Validation via qRT-PCR confirmed the upregulation of mature miR-4762-5p, supporting its potential as a diagnostic biomarker. Pathway enrichment analysis based on transcriptional profiling revealed significant downregulation of immune-related pathways in tubercular uveitis.

CONCLUSION

Unique transcripts are associated with TB uveitis, identifying miR-4762 as a potential diagnostic biomarker. Further, downregulation of transcripts associated with immune-related pathways suggests that Mycobacterium tuberculosis (Mtb) may utilize complex molecular strategies to evade host immune responses and establish infection in the ocular environment.