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H. D. VanGuilder, K. M. Patel, W. M. Freeman, A. J. Barber; Diabetes Reduces Synaptic Proteins and Translational Regulators in Rat Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4974.
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© ARVO (1962-2015); The Authors (2016-present)
Neurodegeneration is an established feature of diabetic retinopathy. This lab has recently demonstrated that as little as one month of streptozotocin (STZ)-diabetes reduces synaptic and dendritic proteins and their mRNAs in rat retina. The impact of diabetes on synaptic connectivity in the retina, however, remains largely unexplored despite clinical evidence suggesting an early disruption of visual signal transmission. The aim of this study was to investigate the impact of diabetes on synaptic protein regulation in the retina.
Retinal synaptosomes were isolated from one-month STZ-diabetic and age-matched control male Sprague-Dawley rats. Samples were lysed and immunoblotted with antibodies to the synaptic proteins synaptophysin, synaptobrevin-2, synapse-associated protein of 25kDa, synapsin I and postsynaptic density-95. mRNA transcripts encoding these proteins were quantified by RT-qPCR. Mechanisms of protein translation were also studied in synaptosomes by immunoblotting and RT-qPCR.
Two whole retinas were used to obtain each synaptosome pellet, containing an average of 90 ± 3.9 µg protein. Electron microscopy determined that the samples were intact synaptosomes containing post-synaptic densities and an abundance of vesicles. Synaptic proteins were enriched in synaptosome samples compared to whole retina. Components of signaling and protein translation mechanisms, including Akt, IRß and eIF2, as well as several synaptic protein mRNAs, were also present. There was significantly less total protein and individual synaptic proteins in retinal synaptosomes isolated from STZ-diabetic rats, compared to controls.
Insulin receptor and Akt signaling components, and protein translation initiation factors are present at retinal synapses, indicating potential local insulin receptor-mediated signaling and regulation of synaptic protein content. Diabetes decreases synapse-associated proteins important to neurotransmission at the synapse, possibly by disrupting translational regulation. These data have broad implications for understanding mechanisms of vision loss in diabetic retinopathy.
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