3',4'-Dihydroxyflavonol Inhibits Fibrotic Response in a Rabbit Model of Glaucoma Filtration Surgery

Int J Mol Sci. 2024 Oct 7;25(19):10767. doi: 10.3390/ijms251910767.

Abstract

Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3',4'-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery (n = 5) or a single intraoperative treatment of MMC (n = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon's layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS.

Keywords: antifibrotic; conjunctival scarring; glaucoma filtration surgery.

MeSH terms

  • Animals
  • Collagen / metabolism
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology
  • Conjunctiva / surgery
  • Disease Models, Animal*
  • Fibrosis*
  • Filtering Surgery* / adverse effects
  • Filtering Surgery* / methods
  • Flavonols* / pharmacology
  • Flavonols* / therapeutic use
  • Glaucoma* / drug therapy
  • Glaucoma* / metabolism
  • Glaucoma* / pathology
  • Glaucoma* / surgery
  • Mitomycin / pharmacology
  • Oxidative Stress / drug effects
  • Rabbits

Substances

  • Flavonols
  • 3',4'-dihydroxyflavonol
  • Collagen
  • Mitomycin