Retinal Transcriptome Analysis in the Treatment of Endotoxin-Induced Uveitis with Tetramethylpyrazine Eye Drops.

Abstract

Purpose: To investigate retinal gene expression of tetramethylpyrazine (TMP) eye drop-treated endotoxin-induced uveitis (EIU) in mice and to explore the mechanisms. Methods: The inflammatory signs of the anterior segment were evaluated, and clinical scores were graded. The retinal transcriptome from the TMP eye drop-treated and the untreated mice was identified by RNA sequencing (RNA-seq) strategy. Differentially expressed genes (DEGs) were validated by real-time PCR. The protein-protein interaction was analyzed using the STRING software. Results: Compared with the TMP-treated group, the inflammatory responses of the untreated control group were much severe and clinical score was remarkably higher (P < 0.001) at 24 h after lipopolysaccharide administration. RNA-seq assay identified 407 DEGs, among which 356 were upregulated and 51 were downregulated. There were 12 upregulated gene ontology terms enriched and 27 upregulated pathways. Seven DEGs, including inflammation-related, complement system-related, and interferon-related genes, were validated using quantitative PCR. Conclusions: TMP exerted anti-inflammatory effect in EIU. Local application of TMP inhibited retinal inflammatory response by regulating the inflammation-related genes, suggesting that TMP may be a potential novel therapeutic drug for ocular inflammation.