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A. Caicedo, D. Espinosa-Heidmann, S.W. Cousins; Glutamate Transporters at Photoreceptor Synapses Are Downregulated after Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3935.
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Purpose: Patients with choroidal neovascularization (CNV) associated with age-related macular degeneration have reduced vision and retinal function as assessed by focal electroretinograms (ERGs; e.g. Terasaki et al., IOVS, 43:1540). A strong reduction of the b-wave of the focal ERG suggests that inner retinal function is mostly affected. We are interested in understanding how CNV-induced changes in visual acuity and focal ERGs correlate with anatomical, biochemical and physiological changes in the retina. We hypothesize that experimental CNV might alter synaptic transmission at photoreceptor cell synapses. Because photoreceptor cells release glutamate, we were particularly interested in examining changes in the expression of molecules involved in glutamate release and uptake. Methods: Laser-induced CNV was induced in 8 month-old mice and, after four weeks, the eyes were removed and sectioned on a cryostat microtome. Vertical eye sections (14 µm) were immunostained for the glutamate transporters GLAST and GLT-1, as well as for the vesicular glutamate transporter BNPI. Results: Retinas of control mice and retinal regions adjacent to the lesions showed immunostaining patterns as described in the literature. By contrast, GLAST and BNPI immunoreactivities markedly changed in retinal regions over CNV lesions. GLAST immunoreactivity translocated within Muller cells leading to markedly reduced immunoreactivity in the outer plexiform layer (where photoreceptor synapses are located) and aberrantly increased expression within the outer nuclear layer. BNPI immunoreactivity almost disappeared from the outer plexiform layer, indicating that vesicular glutamate transporters in photoreceptor synaptic terminals were strongly downregulated. Conclusions: Our results indicate that major changes in synaptic glutatamate transport and uptake occur in the retina overlying CNV. These data suggest that loss of synaptic transmission at photoreceptor synapses might explain changes in focal ERGs and vision loss. We are currently examining how glutamate release by photoreceptor cells is affected by CNV.
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