Tissue Plasminogen Activator as an Antiangiogenic Agent in Experimental Corneal Neovascularization in Rabbits

Anti-vascular endothelial growth factor agents effectively treat age-related macular degeneration and myopic choroidal neovascularization (CNV). Tissue plasminogen activator (tPA), a fibrinolytic compound, is used as an adjuvant to displace submacular hemorrhage and to treat type 2 CNV. The purpose of this study was to investigate in in vitro and in vivo experiments the antiangiogenic impact of tPA itself.

The impact of tPA on the proliferation of human umbilical vein endothelial cells (HUVECs) was assessed by an XTT assay [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]. A basic fibroblast growth factor-impregnated gelatin hydrogel sheet was implanted into the rabbit cornea to induce corneal neovascularization. Immediately postoperatively, tPA or buffered saline solution (control) was injected intravitreally.

The growth and viability of the HUVECs were unaffected by tPA at clinical concentrations. In the control group, the mean lengths of the new vessels were 1.0 ± 0.41, 1.6 ± 0.75, and 3.6 ± 2.1 mm at weeks 1, 2, and 4, respectively. In contrast, tPA significantly (p < 0.01) reduced the corneal neovascularization.

Although tPA has no direct impact on the vascular endothelial cells in vitro, the fibrinolytic effects of tPA might markedly suppress neovascularization in vivo.