The Effect of 0.5% Timolol Maleate on Corneal(Lymph)Angiogenesis in a Murine Suture Model.

PURPOSE: To investigate the anti(lymph)angiogenic and anti-inflammatory effects of 0.5% timolol maleate in a murine corneal suture model.

METHODS: Corneal neovascularization and lymphangiogenesis were compared in groups of mice that underwent corneal suture and were subsequently administered a subconjunctival injection of 0.5% timolol maleate, dexamethasone, or phosphate-buffered saline (PBS). Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction (RT-PCR) was performed to quantify the expression of inflammatory cytokines [TNF-alpha and interleukin (IL)-6], vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, and VEGFR-3.

RESULTS: When corneas from the timolol-treated group were compared to the PBS-treated group, we observed decreases in angiogenesis, lymphangiogenesis, and inflammatory infiltration in the timolol-treated group (P value <0.05 in all respective comparisons). Corneas from the timolol-treated group showed reduced expression of VEGF-A, VEGF-C, TNF-alpha, IL-6, VEGFR-2, and VEGFR-3 compared to corneas from the PBS group (P value <0.05 in all respective comparisons).

CONCLUSION: Blocking adrenergic signaling in the cornea with 0.5% timolol maleate decreased corneal neovascularization and lymphangiogenesis.