Abstract
Purpose: :
It has been previously reported that parvalbumin expression was downregulated in AII amacrine cells, while upregulated in a subset of cone bipolar cells electrically synapse with AII amacrine cell in the streptozotocin–induced diabetic rat retina. In the present study, we aimed to trace biochemical changes of pre–synaptic neurons to parvalbumin expressing AII amacrine cells in rat retina following diabetic injury.
Methods: :
Sprague–Dawley rats aged of 8 weeks were intravenously injected with streptozotocin (60 mg/kg b.w. resolved in 0.05M sodium citrate–HCL buffer, pH 5.5). The animals showing above 300 mg/dl blood glucose levels have been decided to be diabetic. The experimental term of induced diabetes was set at 1, 4, 12 and 24 weeks. Changes of pre–synaptic neurons were evaluated by immunohistochemistry and Western blot analysis with anti–protein kinase C (PKC)–α and anti–tyrosine hydroxylase(TH) antibodies.
Results: :
Rod bipolar cells immunolocalized with PKC–α antibody extended their enlarged axon terminals into stratum 5. In later diabetes, the axon terminals of rod bipolar cell are slightly enlarged. The protein levels of PKC–α were slightly increased along with the duration of diabetes. TH immunoreactive neurons are morphologically classified into two subtypes of amacrine cells in the inner nuclear layer: one has large soma with long and primary dendrites and the other has small soma with dendritic arborization. In the outermost inner plexiform layer, ring–like structures were densely distributed. In diabetic retina, the intensity of TH immunoreactivity in larger neurons was weakened. In accordance with morphological changes, the protein levels of TH were reduced during diabetes.
Conclusions: :
These results demonstrate that TH immunoreactive amacrine cells are more susceptible to diabetic injury than the bipolar cells in the rat retina and suggest that downregulation of parvalbumin expression in AII amacrine cells of diabetic retina is mainly due to dysfunction of pre–synaptic dopaminergic amacrine cells.
Keywords: diabetic retinopathy • amacrine cells • synapse