A p38 MAPK inhibitor improves outcome after glaucoma filtration surgery.

PURPOSE

The aim of this study is to explore the effects of SB 202190, a highly selective p38 MAPK inhibitor, on bleb survival following glaucoma filtering surgery.

MATERIALS AND METHODS

Human Tenon's fibroblasts were treated with SB 202190 (0 to 100 μM) to determine IC50, and cell proliferation and migration. Twenty rabbits were divided into 4 groups (G1-G4): G1 animals received only a trabeculectomy. G2-G4 animals had trabeculectomy plus one of the following subconjunctival adjuvants, given intraoperatively and postoperatively: G2=sham, G3=20 μM SB 202190, and G4=50 μM SB 202190. The blebs were assessed using the Indiana Bleb Appearance Grading Scale. The intraocular pressure (IOP) was expressed as the right to left eye ratio (R/L ratio). For morphometric bleb analysis the JMicrovision software was used.

RESULTS

SB 202190 inhibits human Tenon's fibroblasts proliferation and migration in vitro (IC50=17.2 μM). In vivo subconjunctival application of SB 202190 after glaucoma filtration surgery significantly increases bleb height, bleb extension, and bleb survival time compared with the control. In all groups, the IOP ratio correlates with the fibrotic process. G3 shows a significantly reduced IOP ratio at day 14 compared with the control. Analysis of the bleb histology shows that G3 has a significant smaller fibrosis area compared with G1 and G2. Application of the highest dose (50 μM SB 202190) is associated with hyphema in 2 of 5 animals (40%).

CONCLUSION

Application of SB 202190 significantly improves bleb characteristics and IOP control after filtering glaucoma surgery in a rabbit model.