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Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Rabbit Model of Minimally Invasive Bleb Surgery With PreserFlo
Zoe Pasvanis1,2, Roy C K Kong1,2,3, Elsa C Chan1,2,3
1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
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.
Insights
3',4'-Dihydroxyflavonol (DiOHF) effectively reduced scarring after PreserFlo MicroShunt (PFMS) surgery in rabbits. This novel compound shows potential as a safer antifibrotic agent compared to Mitomycin C (MMC).
Area of Science:
- Ophthalmology
- Glaucoma Surgery
- Wound Healing
Background:
- Minimally invasive bleb surgery (MIBS) success, like PreserFlo MicroShunt (PFMS), is hindered by post-operative bleb fibrosis.
- Current antifibrotic therapy uses off-label cytotoxic agents such as Mitomycin C (MMC).
- This study evaluates 3",4"-Dihydroxyflavonol (DiOHF) as a novel antifibrotic agent in a rabbit model of PFMS surgery.
Purpose of the Study:
- To investigate the anti-scarring properties of DiOHF.
- To compare DiOHF's efficacy against vehicle control and Mitomycin C (MMC).
- To assess DiOHF's impact on fibrosis, oxidative stress, inflammation, and fibroblast activity post-PFMS.
Main Methods:
- Unilateral MIBS with PFMS was performed on 15 New Zealand white rabbits.
- Rabbits were randomized into three groups: vehicle, DiOHF, or MMC.
- Bleb morphology was assessed clinically and histologically (collagen, αSMA, oxidative stress, inflammation) on Day 14.
Main Results:
- DiOHF treatment resulted in decreased vimentin, αSMA, and 3-nitrotyrosine expression compared to vehicle.
- DiOHF blebs showed reduced CD45 expression (inflammation) and less collagen accumulation than vehicle and MMC groups.
- MMC-treated blebs exhibited increased size and ischemia compared to DiOHF and vehicle groups.
Conclusions:
- DiOHF effectively inhibited scarring after PFMS implantation in rabbit eyes.
- DiOHF reduced local oxidative stress, inflammation, and fibroblastic activity.
- DiOHF presents a potentially safer and more effective alternative to MMC for wound modulation in glaucoma surgery.
