Adrenaline blocks key cell cycle genes and exhibits antifibrotic and vasoconstrictor effects in glaucoma surgery

ARISTIDES TAGALAKIS, KX Thong, P Andriesei, J Luo, M Qin, J Ng, P Hysi, C Yu-Wai-Man*

*Corresponding author for this work

Research output: Contribution to journalArticle (journal)peer-review

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Abstract

Adrenaline is a sympathomimetic drug used to maintain pupil dilation and to decrease the risk of bleeding. The aim of this study was to demonstrate if adrenaline could exert antifibrotic effects in glaucoma surgery. Adrenaline was tested in fibroblast-populated collagen contraction assays and there was a dose-response decrease in fibroblast contractility: matrices decreased to 47.4% (P=0.0002) and 86.6% (P=0.0036) with adrenaline 0.0005% and 0.01%, respectively. There was no significant decrease in cell viability even at high concentrations. Human Tenon’s fibroblasts were also treated with adrenaline (0%, 0.0005%, 0.01%) for 24 hours and RNA-Sequencing was performed on the Illumina NextSeq2000. We carried out detailed gene ontology, pathway, disease and drug enrichment analyses. Adrenaline 0.01% upregulated 26 G1/S and 11 S-phase genes, and downregulated 23 G2 and 17 M-phase genes (P<0.05). Adrenaline demonstrated similar pathway enrichment to mitosis and spindle checkpoint regulation. Adrenaline 0.05% was also injected subconjunctivally during trabeculectomy, PreserFlo Microshunt and Baerveldt 350 tube surgeries, and patients did not experience any adverse effects. Adrenaline is a safe and cheap antifibrotic drug that significantly blocks key cell cycle genes when used at high concentrations. Unless contraindicated, we recommend subconjunctival injections of adrenaline (0.05%) in all glaucoma bleb-forming surgeries.
Original languageEnglish
JournalExperimental Eye Research
Early online date8 Jul 2023
DOIs
Publication statusE-pub ahead of print - 8 Jul 2023

Keywords

  • Adrenaline
  • glaucoma surgery
  • RNA-Sequencing
  • cell cycle
  • fibrosis

Research Centres

  • Data Science STEM Research Centre

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