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A. Wenzel, T.A. Afanasieva, M.W. Seeliger, C. Grimm, M. Samardzija, S. Hotop, C.E. Remé; Balance of PEDF and VEGF controls light induced photoreceptor apoptosis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):779.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: PEDF is an anti–angiogenic and neuroprotective factor in the eye. Intravitreally injected recombinant PEDF protects photoreceptors from light damage (Cao W., et al., IOVS, 2001, 42, 1646) and viral delivery of PEDF into the eye protects photoreceptors from degeneration in the RCS rat (Miyazaki et al., Gene Ther., 2003, 10, 1503). Here we tried an alternative route of PEDF delivery to protect photoreceptors from light damage: Systemic delivery of recombinant adenovirus (Ad) encoding PEDF. As PEDF and VEGF act antagonistically in neovascularisation, we furthermore tested the possibility that the balance of PEDF and VEGF is crucial also for the fate of photoreceptors after toxic light exposure. Methods: Mice (Balb/C) were injected i.v. with Ad viruses (10^9 PFU) carrying transgenes (CMV promotor) for mouse PEDF, green fluorescent protein (GFP) or a single chain antibody specific for VEGF (Afanasieva TA. et al., Gene Ther. 2003, 10, 1850). Control mice received no injection. Light exposure (5000lux of white light for 2h) was performed 2 days following the injection. Treatment outcome was assessed by morphology, rhodopsin measurements and ERG. Retinal VEGF content was analyzed by ELISA. Results: Light exposure led to elevated VEGF levels 24 to 48h after light exposure in control mice. Ten, 20 and 30 d after light exposure, control animals and mice treated with Ad–GFP showed severe photoreceptor loss and rhodopsin levels were reduced to 20 and 30% of normal, respectively. Retinal function was severely compromised in these animals. In Ad–PEDF treated mice, photoreceptor loss was dramatically reduced and more than 60% rhodopsin was remaining even 30d after light exposure. Retinal function was better preserved than in non–injected animals exposed to light. Results similar to those for Ad–PEDF treatment were obtained with Ad–single chain VEGF antibody treatment. Discussion: Exposure to toxic levels of light causes an increase of retinal VEGF. Counteracting this increase with systemically expressed single chain antibody against VEGF or increasing PEDF by systemic expression leads to protection against light–induced photoreceptor apoptosis. Both treatments may shift the PEDF / VEGF balance in favor of PEDF. These results raise the possibility that the balance of PEDF and VEGF is not only crucial for angiogenesis but also for photoreceptor survival after exposure to toxic light doses.
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