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Chankee Park, Hae-Young Lopilly Park; Alterations of the Synapse of the Inner Retinal Layers after Chronic Intraocular Pressure Elevation in Glaucoma Animal Model and Modulation by Brain-Derived Neurotrophic Factor. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2412.
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© ARVO (1962-2015); The Authors (2016-present)
Dendrites of retinal ganglion cells (RGCs) synapse with axon terminals of bipolar cells in the inner plexiform layer (IPL). Changes in RGC dendrites and synapses between bipolar cells in the inner retinal layer may critically alter the function of RGCs in glaucoma. Recently, synaptic plasticity has been observed in the adult central nervous system, including the outer retinal layers. However, few studies have focused on changes in the synapses between RGCs and bipolar cells in glaucoma. In the present study, we used a rat model of ocular hypertension induced by episcleral vein cauterization to investigate changes in synaptic structure and protein expression in the inner retinal layer at various time points after moderate intraocular pressure (IOP) elevation and modulation using brain-derived neurotrophic factor (BDNF) was evaluated.
Adult male Sprague-Dawley rats (7-8 weeks old, 250-300 g) were used in this study. All animal experiments complied with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research. Three episcleral veins were cauterized by a standard technique. Ribbon synapses in the IPL were quantified and structurally evaluated in retinal sections by transmission electron microscopy at 8 weeks post-surgery. To evaluate synaptic vesicles, retinal expression of synaptophysin and PSD-95 were assessed. BDNF was injected intravitreously.
Synaptophysin, a presynaptic vesicle protein, increased throughout the IPL, outer plexiform layer, and outer nuclear layer after IOP elevation. Increased synaptophysin after IOP elevation was expressed in bipolar cells in the innermost IPL. The RGC marker, SMI-32, co-localized with synaptophysin in RGC dendrites and were significantly increased at 1 week and 4 weeks after IOP elevation. Ribbon synapses in the IPL were quantified and structurally evaluated in retinal sections by transmission electron microscopy. After BDNF injection, the number of ribbon synapses and synaptic vesicle proteins increased.
There are attempts to increase synaptic vesicle proteins in the retina after IOP elevation and its was enhanced using BDNF. Further treatment to strengthen or increase the number of synapses between RGCs and bipolar cells would delay functional loss in glaucoma.
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