Lo Phey Feng, Gunawan Merry, Yap Zhu Li, Leong Carol, Kwek Fuxuan, Varadarajan Jayasudha, Wang Xiaomeng, Kageyama Masaaki, Wong Tina T
Singapore Eye Research Institute, Singapore, Singapore.
Santen-SERI Open Innovation Centre, Singapore, Singapore.
Transl Vis Sci Technol. 2025 Jun 2;14(6):6. doi: 10.1167/tvst.14.6.6.
To evaluate different routes of valproic acid (VPA) administration in modulating various phases of wound healing events after minimally invasive bleb surgery (MIBS).
Thirty New Zealand White rabbits underwent surgical implantation of PRESERFLO MicroShunts. Animals were divided into treatment groups of mitomycin C (MMC) 0.4 mg/mL, MMC 0.1 mg/mL, VPA 1 mg/mL, and VPA 30 mg/mL. Treatments with topical and subconjunctival administration were investigated in the combination groups of low-dose MMC (0.1 mg/mL) and VPA. IOP was measured and slit-lamp photographs were taken weekly. Fibrotic gene expression was analyzed in the bleb by quantitative polymerase chain reaction and western blot. Histology was performed following sacrifice on day 28.
Low-dose MMC (0.1 mg/mL) combined with VPA resulted in prolonged bleb survival to day 28. This was associated with reduced collagen 1 and fibronectin gene and protein expression (P < 0.05). There was also a favorable extracellular matrix structure on histological analysis due to the presence of fine immature collagen fibrils surrounding the shunt opening. Intraocular pressure lowering was seen, with a reduction of 20% from baseline IOP until day 14. Both topical and subconjunctival administration of VPA demonstrated similar outcomes, with no overt side effects observed throughout the experimental period at different doses or dosing regimens.
VPA is a versatile and effective adjunctive agent that can be used in combination with low-dose MMC to produce favorable bleb characteristics in MIBS.
VPA is both efficacious and safe as an antifibrotic agent, and different routes of administration are available to target different stages of fibrosis after filtration surgery.
评估丙戊酸（VPA）不同给药途径对微创滤过泡手术（MIBS）后伤口愈合各阶段的调节作用。
30只新西兰白兔接受了PRESERFLO微型分流器的手术植入。动物被分为丝裂霉素C（MMC）0.4mg/mL、MMC 0.1mg/mL、VPA 1mg/mL和VPA 30mg/mL治疗组。在低剂量MMC（0.1mg/mL）和VPA联合组中研究了局部和结膜下给药治疗。每周测量眼压并拍摄裂隙灯照片。通过定量聚合酶链反应和蛋白质印迹分析滤过泡中的纤维化基因表达。在第28天处死动物后进行组织学检查。
低剂量MMC（0.1mg/mL）与VPA联合使用可使滤过泡存活时间延长至第28天。这与胶原蛋白1和纤连蛋白基因及蛋白表达降低有关（P<0.05）。组织学分析还显示，由于分流开口周围存在细小的未成熟胶原纤维，细胞外基质结构良好。眼压降低，从基线眼压降低20%，持续至第14天。VPA局部和结膜下给药均显示出相似的结果，在整个实验期间，不同剂量或给药方案均未观察到明显副作用。
VPA是一种通用且有效的辅助药物，可与低剂量MMC联合使用，在MIBS中产生良好的滤过泡特征。
VPA作为抗纤维化药物既有效又安全，并且有不同的给药途径可针对滤过手术后纤维化的不同阶段。
