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

J Ocul Pharmacol Ther. 2019 May;35(4):235-244. doi: 10.1089/jop.2018.0105. Epub 2019 Apr 17.

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.

Keywords: endotoxin-induced uveitis; interferon; retina; tetramethylpyrazine; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endotoxins / administration & dosage
  • Female
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Mice
  • Mice, Inbred BALB C
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / pharmacology
  • Ophthalmic Solutions / therapeutic use*
  • Protective Agents / administration & dosage
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Retina / drug effects*
  • Retina / metabolism
  • Transcriptome / drug effects*
  • Uveitis / chemically induced
  • Uveitis / drug therapy*
  • Uveitis / genetics

Substances

  • Endotoxins
  • Ophthalmic Solutions
  • Protective Agents
  • Pyrazines
  • tetramethylpyrazine