acetogenins and Corneal-Neovascularization

Previous studies demonstrated that annonaceous acetogenin (AA) was an antitumor drug with anti-angiogenic activity. However, the effect of AA on ocular neovascular disorders remains unclear. The aim of the present study is to explore the effect of AA092, an annonaceous acetogenin mimetic, on corneal neovascularization (CNV). In a mouse model of alkali-induced CNV, topical application of AA092 to the injured corneas attenuated CNV. In addition, in vivo treatment with AA092 down-regulated the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1, EGF but up-regulated the expression of the anti-angiogenic factors Thrombospondin-1 (Tsp-1), Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, AA092 inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human microvascular endothelial cells (HEMC-1) in vitro. These data indicate that AA092 has therapeutic potential for angiogenesis-associated diseases such as CNV.

Topics: Acetogenins; Alkalies; Animals; Annonaceae; Biomimetics; Cell Line; Cornea; Corneal Neovascularization; Disease Models, Animal; Endothelium, Vascular; Female; Humans; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C