Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Rabbit Model of Minimally Invasive Bleb Surgery With PreserFlo MicroShunt.

Abstract

BACKGROUND: The success of minimally invasive bleb surgery (MIBS) such as the PreserFlo MicroShunt (PFMS) is limited by post-operative bleb fibrosis. Current clinical practice prescribes the use of off-label cytotoxic antimetabolites such as Mitomycin C (MMC) as antifibrotic therapy. This study investigates the anti-scarring properties of a novel compound, 3',4'-Dihydroxyflavonol (DiOHF) in a rabbit model of PFMS filtration surgery. METHODS: Fifteen New Zealand white rabbits underwent unilateral MIBS with PFMS. Treatment was randomised to the following groups: (1) vehicle (n = 5), (2) DiOHF (n = 5), both applied three times daily for 2 weeks or (3) a single dose of MMC administered intraoperatively (n = 5). Blebs were photographed post-operatively on Days 0, 7 and 14 for clinical examination. Eyes were harvested on Day 14 and processed for immunohistochemical tissue staining to assess collagen deposition, expression of αSMA, oxidative stress, fibroblast activity, angiogenesis and inflammation in the conjunctiva/Tenon's layer. RESULTS: At 2-weeks post-surgery, MMC blebs were larger and more ischaemic than other treatments (Bleb size: MMC vs. DiOHF, p = 0.0098; MMC vs. vehicle, p = 0.0001. Ischaemia: p = 0.0004 for both). Compared to vehicle control, DiOHF blebs expressed decreased vimentin (p = 0.0099), αSMA (p = 0.0231) and 3-nitrotyrosine (p = 0.0410) after 2 weeks. DiOHF blebs expressed less CD45 than other treatments (DiOHF vs. Vehicle, p = 0.0013; DiOHF vs. MMC, p = 0.0232) and less collagen accumulation (DiOHF vs. vehicle, p = 0.0512). There was no difference in CD31 expression between treatment groups. CONCLUSIONS: DiOHF inhibited scarring following implantation of PFMS in rabbit eyes by reducing local oxidative stress, inflammation and fibroblastic activity. DiOHF may be a safer and more effective wound modulating agent than the conventional use of MMC.