Abstract：
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.
摘要：
链脲佐菌素（STZ）诱导的啮齿动物模型是糖尿病视网膜病变（DR）临床前药物发现中最常用的模型之一。然而,实验读数的标准化和验证在很大程度上是缺乏的。本系统评价的目的是确定和比较STZ诱导的DR的最有用的读数，并根据我们的发现为未来的研究设计提供建议。我们使用两个主要数据库进行了系统的搜索，PubMed和EMBASE。仅选择描述STZ诱导的DR的文章，这些文章描述了功能和结构读数。我们还评估了偏倚的风险，并分析了选定研究中的定性数据。我们确定了21项符合纳入/排除标准的研究，使用大鼠或小鼠，研究周期为2至24周。用于定义高血糖的葡萄糖水平阈值在研究之间不一致。然而,大多数研究使用250或300.6mg/dL作为高血糖的定义标准.所有纳入的研究均进行了视网膜电图（ERG），并报告了a-，b-,或c波和/或振荡电位振幅。谱域光学相干层析成像和荧光素血管造影，以及免疫组织化学和组织病理学分析显示视网膜厚度减少，血管变化,和炎症的存在。偏倚风险评估表明，由于缺乏报告或正确遵循程序，所有研究都有较高的偏倚风险。我们的系统评价强调，ERG代表了STZ模型中最一致的功能读数。然而,由于偏见的高风险，在解释这些研究时必须谨慎。
