Flt3 Regulation in the Mononuclear Phagocyte System Promotes Ocular Neovascularization

Figure 6

Effect of intraocular injection of AC220 in double-transgenic mice overexpressing VEGF in photoreceptors (rho/rtTA-TRE/VEGF mice). Four-week-old adult rho/rtTA-TRE/VEGF mice received an intravitreal injection of 1 μg of AC220 (in 1 μl PBS) in one eye and 1 μl PBS in the contralateral eye. The animals then received doxycycline at 2 mg/ml in drinking water. (a) After five days, non-AC220-treated retinas were lysed, and phosphorylated Flt3 amounts were measured by the ELISA method. Phosphorylated Flt3 amounts in RD model retinas were higher than those in both wild-type and no-doxycycline-treated retinas. (b) Five days after initiation of doxycycline treatment, ocular sections showed no retinal detachment (no RD), partial retinal detachment (PRD), or total retinal detachment (TRD). (c) Intraocular injection of AC220 or PBS in doxycycline-treated rho/rtTA-TRE/VEGF mice. Retina samples were examined under an operating microscope in a blinded manner, to determine if there was TRD, PRD, or no RD. In AC220-treated mice, 25% of eyes had TRD, and 50% of eyes injected with PBS had TRD. The asterisk “” indicates that the incidence of RD in AC220-injected eyes was significantly reduced than that of the PBS-injected counterparts ( by chi-square). This suggests that intravitreal injection of 1 μg AC220 significantly reduced TRD.

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