Abstract
Purpose :
Diabetic retinopathy (DR) is one of the leading causes of visual impairment and blindness worldwide. To date, murine models of streptozotocin (STZ)-induced diabetes have been widely used for experimental DR research. However, long-term maintenance of STZ mice for DR development is required, furthermore ischemic phenotypes are limited to be detected in the STZ-induced diabetic retina. Recently, common carotid artery occlusion (CCAO) has been gradually introduced to induce retinal ischemic insults in murine models. Nonetheless, its pathologic effect has not been examined in experimental DR. Therefore, in this study, we aimed to investigate the pathologic effects of CCAO on retinal inflammatory responses in adult STZ mice.
Methods :
STZ (dissolved in sodium citrate buffer at pH 4.5; 90 mg/kg) was intraperitoneally injected into adult male mice (5 weeks old; C57BL/6) for two consecutive days. Permanent CCAO was performed on STZ mice (blood glucose levels; greater than 300 mg/dL) using 6–0 silk sutures five days after the injection. Seven days after CCAO, retinal samples were obtained and subjected to quantitative PCR (qPCR) and immunohistochemistry (IHC) analyses to observe early inflammatory responses in the retina of STZ mice.
Results :
Significant increases in pathologic inflammatory cells stained by isolectin GS-IB4 were detected in the CCAO/STZ retina (IHC; 19.2-fold increase, p < 0.05, compared with the naïve retina), while its phenotype was not observed in the only STZ retina (IHC; p > 0.05, compared with the naïve retina). Dramatic increases in immune responsive gene expressions were shown in the CCAO/STZ retina (qPCR; Iba1: ionized calcium-binding adapter molecule 1, Vegfa: vascular endothelial growth factor-a, Tlr2: toll-like receptor 2; 1.6-fold increase, 1.2-fold increase, 1.6-fold increase, p < 0.05, compared with the naïve retina, respectively), while their changes were not significantly seen in the only STZ retina (qPCR; p > 0.05, compared with the naïve retina).
Conclusions :
Our current data suggest promising possibilities for early induction of ischemic inflammatory responses in the retina of STZ mice through the permanent CCAO surgery, which could further facilitate experimental DR research.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.