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Nathan Lambert, Xiaohui Zhang, Judd Cahoon, Hironori Uehara, Balamurali Ambati; Effects of COMP-Ang1 on Neovascularization in a Mouse Model of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1187.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of COMP-Ang1 on vessel proliferation and VEGF levels in a mouse model of AMD
C57Bl6 mice received 1µL subretinal injections of PBS or a viral vector (AAV2) expressing LacZ, GFP, or COMP-Ang1. 1 month later mice underwent laser-induced CNV (532-nm diode laser spots, 140mW, 100msec, 50µm). Laser lesions were induced at locations of 3, 6, 9, and 12 o’clock 2-3 disc diameters from the optic nerve in each eye. One week after laser CNV, mice eyes were enucleated, the choroid was stained for CD31 markers using immunohistochemistry, and then prepared as choroidal flatmounts. CNV volume was assessed using confocal microscopy and quantified using Image J software.
CNV volume was significantly decreased in mice with AAV2.COMP-Ang1 treatment compared with AAV2.GFP, AAV2.LacZ, and PBS groups. The CNV volume for the various groups was as follows: +AAV2.COMP-Ang1 6.36 ± 1.94 X 104 µm3 (n=31)* +AAV2.LacZ 15.75 ± 4.91 X 104 µm3 (n=38) +AAV2.GFP 21.32 ± 4.57 X 104 µm3 (n=30) +PBS 16.12 ± 3.155 X 104 µm3 (n=40) COMP-Ang1 decreased laser CNV volume nearly 2.5x when compared to PBS (P=0.017) and AAV2.LacZ (P=0.1) and over 3.3x compared to AAV2.GFP (P=0.003).
These findings provide evidence that AAV2 expression of COMP-Ang1 decreases laser CNV volume in a mouse model. Some limitations to this study include size and shape of laser-induced CNV growth. Further studies will address the effects COMP-Ang1 on VEGF levels.
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