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Sudhakar A. Yakkanti, Venugopal Gunda, Raj K. Verma, Chandra S. Boosani; Different Mechanisms in Regulation of Laser Induced CNV by Arresten. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5829.
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Among other vascular diseases, choroidal neovascularisation is the primary cause of blindness in a variety of common retinal diseases including retinopathy of prematurity, age related macular degeneration, proliferative diabetic retinopathy etc., and angioinhibitory therapies are gaining increased significance for the treatment of these ocular diseases. In our present study we tested the angioinhibitory activity of arresten and analyzed both in in-vitro and in-vivo for its ability to inhibit laser induced choroidal neovascularisation in mice.
Mouse choroidal endothelial cells (MCEC) were treated with different doses of arresten to study inhibition of in-vitro cell proliferation, migration and tube formation. Activation of Matrix metalloproteinase-2 (MMP-2) and MMP-2/arresten complex formation were studied using three different methods that include gelatin zymography, Immunobloting and ISCO gradient analysis. Through in-vivo system in mice, the angioinhibitory effects of arresten were studied by laser induced choroidal neovascularization with subsequent infection by recombinant adenovirus that secretes arresten.
Arresten demonstrated inhibition of vital cellular functions such as proliferation, migration, and tube formation in-vitro in MCECs. Arresten binds to the pro-MMP-2 and inhibits its activation mediated by both membrane-type-1 MMP and 4-amino-phenyl mercuric acetate. Adenoviruses secreted arresten showed significant inhibition of laser induced CNV in mice, besides activation of circulating MMP-2 in-vivo.
Arresten shows two distinct integrin dependent and independent regulatory mechanisms of angioinhibitory effects in mice both in in-vitro and in-vivo.
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