Anti-proliferative effect of olmesartan on Tenon's capsule fibroblasts

AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon’s capsule, both in vitro and in vivo.· METHODS: Human primary Tenon’s capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium(MTT) method.Real-time PCR was performed to analyze changes in m RNA expressions of the fibrosis-related factors: matrix metalloproteinase-2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-1,2) and proliferating cell nuclear antigen(PCNA). Thirty rabbits were divided into5 groups(3, 7, 14, 21, and 28d). A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson’s trichrome to compare the neovascularization in the subconjunctiva area.·RESULTS: In vitro, cultured Tenon’s capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced m RNA expressions of MMP-2 and PCNA but increased m RNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3rd, 7th, 14 thand 21stdays demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28 thday group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson’s trichrome observation.·CONCLUSION: By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery.