Abstract
Purpose: :
Neurodegeneration is a pathological feature of diabetic retinal neuropathy. One key element of neurodegeneration is a reduction in the number of synaptic connections between neurons. The aim of this study was to test the hypothesis that diabetes decreases the expression of specific synaptic and structural proteins in the rat retina.
Methods: :
Antibodies were used to detect synaptophysin, synapsin I, vesicle–associated membrane protein 2 (VAMP2), and postsynaptic density (PSD95), in retinas from three–month streptozotocin–diabetic and age–matched control male Sprague–Dawley rats, by western and immunohistochemistry with confocal microscopy. mRNA content for the same genes was quantified by RT–qPCR. ß–actin was used as an endogenous control in all assays.
Results: :
Diabetes significantly decreased synaptic, but not ß–actin, protein content detected by western blotting. RT–qPCR demonstrated similar significant decreases in mRNA transcript for these proteins. Synaptic protein immunoreactivity in retinal sections from streptozotocin–diabetic rats was decreased in both the inner and outer plexiform layers, accompanied by similar decreases in neurofilament immunoreactivity, compared to controls. Decreased immunoreactivity for all synaptic proteins was most apparent in the outer plexiform layer, with the greatest decreases observed in synapsin I and PSD95.
Conclusions: :
Synaptic proteins and mRNA transcripts are significantly decreased after three months of streptozotocin–induced diabetes. These data suggest that a loss of synaptic function may contribute to impaired neurotransmission and vision loss in diabetes.
Keywords: diabetic retinopathy • diabetes • synapse