Fig. 4.

TM601 suppresses VEGF-induced subretinal neovascularization (NV) in rhodopsin promoter/VEGF (rho/VEGF) transgenic mice. Between P7 and P21 rho/VEGF mice were given daily periocular injections of 3 μl of vehicle or vehicle containing 150 μg of TM601. Mice were perfused with fluorescein-labeled dextran at P21. Retinal flat mounts from control, vehicle-treated eyes visualized with the photoreceptor side facing up showed extensive NV on the outer surface of the retina although it is difficult to see at the magnification that allows visualization of the entire retina because the normal retinal vessels are in the background (A). Higher magnification views (B,C) of the boxed region in (A) provides an arrow depth of field so that only the NV is in focus and the numerous tufts of NV that are partially surrounded by dark retinal pigmented epithelial cells are easily seen (C, arrows). Retinal flat mounts from TM601-injected eyes show much less NV (D); higher magnification of the boxed region in (D) shows few tufts of NV on the outer surface of the retina (E,F, arrows). Image analysis with the investigator masked with respect to treatment group showed that the mean (±SEM) area of NV per retina was significantly less fore yes treated with TM601 compared to controls (G). *P = 0.017 for difference from control by mixed-effects model.