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Tina Wong, Li Zhen Toh, Stephanie Chu, Li Fong Seet; Valproic Acid Reduces Inflammation following Experimental Glaucoma Surgery. Invest. Ophthalmol. Vis. Sci. 2018;59(9):477.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously demonstrated that valproic acid (VPA) was effective in suppressing collagen production in conjunctival wound healing. The purpose of this study aims to further determine the effect of VPA on the inflammatory response following experimental glaucoma filtration surgery (GFS).
Following GFS in the mouse, VPA at 300 μg/ml in 5 μl volume was injected subconjunctivally adjacent the operated site at the end of surgery . PBS was injected in parallel experiments as controls. Blebs were harvested and pooled into 5 groups (n=5) on day 2 post-surgery to assess the inflammatory response, which is measured by cytokine levels, macrophage infiltration and capacity of VPA to suppress the effects of archetypal tumor necrosis factor-alpha, TNF-α, on primary mouse conjunctival fibroblasts. Cytokines were determined using the MCYTOMAG-70K multiplex assay. Macrophages were measured by flow cytometry analysis of CD45/ F4/80-labeled cells. Mouse conjunctival fibroblasts were treated with TNF-α for 48 h before the culture supernatants were recovered for cytokine analysis. Statistical analyses were performed by using either the two-tailed Student’s t-test or one-way ANOVA.
VPA-treated blebs contained significantly less chemokines (CXCL1 and CCL2), interleukins (IL-1α, IL-1β, -2, -5, -6, -9, -10, and -15), and cytokines (GM-CSF and M-CSF). Notably, IL-5, -6, -10 were reduced by more than 2-fold compared to PBS controls. VPA also reduced the recruitment of CD45+F4/80+ cells by 3-10% (mean 6.5% reduction, p=0.0055). In fibroblasts co-treated with TNF-α, VPA significantly suppressed TNF-α induction of chemokines (CCL2, CCL5, and CCL10), interleukins (IL-1α, IL-1β, -2, -5, -10, -12 and -15) and other cytokines (VEGF, IFN-γ). Comparing TNF-α alone with TNF-α and VPA combined treatment, CCL5 was the most suppressed chemokine, by 4.89-fold, (p=3.70e-15).
VPA has the capacity to suppress the inflammatory response by reducing the production of a myriad of proinflammatory chemokines and cytokines as well as the recruitment of macrophages following conjunctival wounding. This property, in conjunction with its capacity to suppress collagen production post surgery, proposes VPA to be an effective adjunct to glaucoma filtration surgery for improving surgical success through its actions on the key two stages of wound healing.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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