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W. F. Robinson, H. D. VanGuilder, T. S. D’Cruz, A. B. El-Remessy, A. J. Barber; Synapsin 1 Protein Expression and Phosphorylation Are Compromised by Diabetes in Rodent and Human Retinas. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4920. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Several proteins critical to neurotransmitter vesicle movement and docking, including synapsin 1, are depleted in rat retinas after 1 and 3 months of streptozotocin (STZ) diabetes. Synapsin 1 phosphorylation initiates neurotransmitter vesicle movement, so the expression of synapsin 1 in postmortem samples of retinas from humans with diabetes was compared to rats and mice.
Diabetes was induced in male Sprague-Dawley rats by i.p. streptozotocin (65 mg/kg) and compared to non-diabetic age-matched controls. Male Ins2Akita/+ diabetic mice were compared to wild-type littermates. Human retinas were acquired from the National Disease Research Institute and Georgia Eye Bank. Protein content and phosphorylation were quantified by immunoblotting whole retina lysates, standardized to actin content and expressed as % control.
The ratio of phospho-synapsin/total synapsin in retinas of 1-month STZ-diabetic rats was 83% of age-matched controls (p<0.05), and this effect was not present in STZ-diabetic rats given insulin. Similarly, total synapsin 1 and the phospho-synapsin/total synapsin ratio were less than controls in Ins2Akita /+ diabetic mice. In synaptosomes from STZ-diabetic rat retinas there was significantly less evoked synapsin 1 phosphorylation compared to controls (p<0.01). In postmortem human retinas the protein content of synapsin 1, and other neuronal proteins (synaptophysin, SNAP25 and neurofilament) was depleted compared to non-diabetic donors.
Diabetes reduces the protein content and basal phosphorylation of synapsin 1 in retinas of mice and rats, and this is reversible with systemic insulin. Synapsin 1 phosphorylation evoked by membrane depolarization was reduced by diabetes, suggesting that the capacity to phosphorylate this protein in response to synaptic activity is compromised. Postmortem retina data suggest that similar changes may occur in humans with diabetes.
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