2008
DOI: 10.1111/j.1460-9568.2008.06322.x
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Diabetes downregulates presynaptic proteins and reduces basal synapsin I phosphorylation in rat retina

Abstract: Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested the hypothesis that diabetes decreases the retinal expression of presynaptic proteins involved in synaptic function. The protein and mRNA contents for synapsin I, synaptophysin, vesicle-associated membrane protein 2, synaptosomal-associated protein of 25 kDa and postsynaptic density protein of 95 kDa were measured by immunohistochemistry, immunoblotting and real-time quantitative … Show more

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Cited by 86 publications
(81 citation statements)
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References 93 publications
(83 reference statements)
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“…We continue to confirm and validate further retinal gene and protein expression changes to gain deeper insight into DR disease processes. 29 In addition, this biomarker panel provides further support of the hypothesis that DR is a feed forward cycle of nutrient overload leading to chronic inflammation, neurodegeneration and compromised blood-retinal barrier function. 32 Future studies will use this biomarker panel in preclinical research of potential therapeutics to monitor disease models and gauge pharmacoefficacy, with the expectation that effective treatments will alter the DR gene expression biomarker panel signature.…”
Section: Discussionmentioning
confidence: 79%
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“…We continue to confirm and validate further retinal gene and protein expression changes to gain deeper insight into DR disease processes. 29 In addition, this biomarker panel provides further support of the hypothesis that DR is a feed forward cycle of nutrient overload leading to chronic inflammation, neurodegeneration and compromised blood-retinal barrier function. 32 Future studies will use this biomarker panel in preclinical research of potential therapeutics to monitor disease models and gauge pharmacoefficacy, with the expectation that effective treatments will alter the DR gene expression biomarker panel signature.…”
Section: Discussionmentioning
confidence: 79%
“…At harvest, diabetic rats were hyperglycemic and underweight compared with controls as with previous assessments. 19,[27][28][29] Treatment with subcutaneous slow-release insulin pellets for the second half of the diabetic period reduced blood glucose levels, and diabetic animals receiving insulin weighed more than untreated diabetic animals. These data and the methods described are representative of experiments performed by the Penn State JDRF Diabetic Retinopathy Center Animal Models Core since 2003.…”
Section: Bioinformatic and Statistical Methodsmentioning
confidence: 99%
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“…One explanation for these reductions is that a cumulative loss of amacrine or bipolar cells by apoptosis caused the reduction in tissue volume [1], but the loss of the inner plexiform layer suggests that there was also an accompanying reduction on the volume of dendrites and synaptic connections. To test this possibility the retinas of diabetic rats were labeled by immunofluorescence for several protein markers of synapses, including synaptophysin, which is an abundant presynaptic vesicle protein in retina and brain [43]. The results demonstrated that the protein content of synaptophysin and several other synaptic proteins was significantly reduced after 1 and 3 months of streptozotocin-induced diabetes in rats.…”
Section: Degenerative Changes In Synapses and Neuron Morphology Accommentioning
confidence: 98%
“…The size and density of synaptophysin-immunoreactive puncta were reduced in the plexiform layers. The loss of synaptic proteins in retinal synaptosomes was accompanied by decreased mRNA content after 1 month of diabetes; therefore, diabetes may increase local degradation rate of presynaptic proteins at retinal synapses and also that of their mRNA (VanGuilder et al, 2008). Indeed, synaptophysin mRNA translation continues at a higher rate after the induction of diabetes as a compensatory mechanism of the reduction of the mature protein.…”
Section: P0585mentioning
confidence: 99%