The STZ-induced diabetic rat as a model for studying neuronal pathologies of diabetic retinopathy
Abstract
Purpose
Diabetic retinopathy (DR) is a sight-threatening complication of diabetes and a leading cause of blindness in adults. Current therapies target late-stage vascular dysfunction of DR. However, DR is not a vascular disease per se, but is also characterized by chronic neurodegeneration. To identify neuroprotective treatments, it is critical to utilize appropriate animal models reflecting a hyperglycemia-dependent loss of retinal function. Here we report a comprehensive characterization of the STZ-induced diabetic rat as a model for neuronal dysfunction in DR.
Methods
Hyperglycemia was induced in Brown Norway rats upon STZ treatment. Blood glucose levels were monitored regularly and insulin levels were measured at study termination. To investigate different aspects of retinal function, dark- and light-adapted flash and flicker electroretinograms were recorded at 4 and 7 weeks post STZ application, respectively. One group of animals received insulin treatment for antagonizing the effects of hyperglycemia.
Results
STZ treatment led to decreased insulin and increased blood glucose levels. Hyperglycemia caused functional impairments of both rod- and cone-driven pathways on the level of the outer as well as the inner retina, which could be partially rescued by insulin treatment. Overall, the degree of functional impairments correlated with increasing blood glucose levels.
Conclusions
The STZ-induced diabetic rat model is characterized by a hyperglycemia-dependent dysfunction of retinal neurons. Thus, this model is an attractive tool for investigating novel mechanisms underlying DR.
