Structure–Function Relationships in the Rodent Streptozotocin-Induced Model for Diabetic Retinopathy: A Systematic Review

The streptozotocin (STZ)-induced rodent model is one of the most commonly employed models in preclinical drug discovery for diabetic retinopathy (DR). However, standardization and validation of experimental readouts are largely lacking. The aim of this systematic review was to identify and compare the most useful readouts of STZ-induced DR and provide recommendations for future study design based on our findings. We performed a systematic search using 2 major databases, PubMed and EMBASE. Only articles describing STZ-induced DR describing both functional and structural readouts were selected. We also assessed the risk of bias and analyzed qualitative data in the selected studies. We identified 21 studies that met our inclusion/exclusion criteria, using either rats or mice and study periods of 2 to 24 weeks. Glucose level thresholds used to define hyperglycemia were inconsistent between studies, however, most studies used either 250 or 300.6 mg/dL as a defining criterion for hyperglycemia. All included studies performed electroretinography (ERG) and reported a reduction in a-, b-, or c-wave and/or oscillatory potential amplitudes. Spectral-domain optical coherence tomography and fluorescein angiography, as well as immunohistochemical and histopathological analyses showed reductions in retinal thickness, vascular changes, and presence of inflammation. Risk of bias assessment showed that all studies had a high risk of bias due to lack of reporting or correctly following procedures. Our systematic review highlights that ERG represents the most consistent functional readout in the STZ model. However, due to the high risk of bias, caution must be used when interpreting these studies.