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Published on: May 11, 2011
Effect of valproic acid on functional bleb morphology in a rabbit model of minimally invasive surgery
Zhu Li Yap1, Li-Fong Seet2, Stephanie Wl Chu3
1Department of Ophthalmology, Singapore Eye Research Institute, Singapore.
Purpose:
To determine the effect of valproic acid (VPA) on bleb morphology and scar characteristics in a rabbit model of minimally invasive glaucoma surgery (MIGS).
Methods:
Nine New Zealand white rabbits were subjected to MIGS with intraoperative implantation of the PreserFlo MicroShunt. Rabbits were then administered with subconjunctival injections of phosphate buffered saline (PBS) (n=4) or with VPA (n=5). Bleb morphology was examined by slit-lamp biomicroscopy and in vivo confocal microscopy. Postoperative day 28 tissues were examined by immunohistochemical evaluation and label-free multiphoton microscopy to visualise the collagen matrix, by terminal deoxynucleotidyl transferase dUTP nick-end labelling assay and immunofluorescent labelling for Ki67 expression to detect apoptosis and cell growth, and by real-time quantitative PCR to measure Col1a1, Fn, and Smad6 transcript expression.
Results:
VPA-treated blebs were detectable on day 28, while the PBS-treated blebs were not detectable by day 14. VPA-treated blebs were diffuse, extended posteriorly with near normal conjunctival vascularity and featured a combination of reticular/blurred stromal pattern with evidence of relatively large stromal cysts. Instead of the deposition of thick, disorganised collagen fibres characteristic of the PBS bleb, the VPA bleb contained conspicuously thinner collagen fibres which were associated with similarly thinner fibronectin fibres. In corroboration, Col1a1 and Fn mRNA expression was reduced in the VPA blebs, while increased Smad6 expression implicated the disruption of the transforming growth factor beta pathway. Apoptosis and cell growth profiles appeared similar with both treatments.
Conclusions:
The results support the application of VPA to enhance bleb morphology associated with good bleb function in MIGS with no apparent cytotoxicity.
Insights
Valproic acid (VPA) improved bleb morphology and function after glaucoma surgery in rabbits. VPA enhanced bleb visibility and reduced scar tissue without apparent cell damage.
Area of Science:
- Ophthalmology
- Glaucoma Research
- Surgical Innovation
Background:
- Minimally invasive glaucoma surgery (MIGS) aims to reduce intraocular pressure.
- Bleb scarring is a common complication that can impair surgical success.
- Valproic acid (VPA) is being investigated for its potential antifibrotic properties.
Purpose of the Study:
- To evaluate the impact of VPA on bleb morphology and scar tissue formation after MIGS in a rabbit model.
- To assess the effect of VPA on key molecular markers of fibrosis and wound healing.
Main Methods:
- Rabbits underwent MIGS with PreserFlo MicroShunt implantation.
- Subconjunctival injections of VPA or phosphate-buffered saline (PBS) were administered.
- Bleb morphology was assessed using microscopy; scar characteristics were analyzed via immunohistochemistry and gene expression analysis.
Main Results:
- VPA-treated blebs remained detectable longer than PBS-treated blebs.
- VPA promoted thinner collagen and fibronectin fibers, reducing scar tissue.
- VPA decreased COL1A1 and FN mRNA expression and increased SMAD6, indicating TGF-β pathway modulation.
Conclusions:
- VPA enhances bleb morphology and function in MIGS.
- VPA treatment appears to mitigate scar formation without cytotoxicity.
- VPA shows promise for improving outcomes in glaucoma surgery.
