Unilateral Common Carotid Artery Occlusion in Adult Mice with Streptozotocin Comorbidity Leads to Early Retinal Inflammation

Diabetic retinopathy (DR) is a leading cause of visual impairment. To better understand the pathology, clinically relevant experimental models are needed. Widely used DR models (especially streptozotocin (STZ)-induced) require extended timeframes to reach DR phenotype endpoints and lack ischemic phenotypes, which are in contrast to the human condition. Unilateral common carotid artery occlusion (UCCAO) could provide a retinal ischemic insult. We explored the pathologic synergistic effects of UCCAO in STZ mice. STZ (90 mg/kg) was injected intraperitoneally into adult C57BL/6 mice for three days. Four weeks later, right UCCAO was performed. One week after UCCAO, retinal samples were stained with isolectin B4 to analyze cellular and vascular changes. Retinal samples were obtained one day and one week after UCCAO and quantitative PCR (qPCR) were performed to observe inflammatory and ischemic responses. Only the STZ UCCAO group showed increased inflammatory cells. STZ UCCAO retina demonstrated a significant difference in capillary and large vessel size compared to other groups. At one day and one week, there was a change in mRNA expressions in inflammatory genes <i>Ccl2</i>, <i>Ccl12</i>, <i>Bnip3</i>, <i>Pdk1, Hsp25</i>, and <i>Vegfa</i> in the STZ UCCAO group compared to other groups. Our model can serve as an accelerated DR model for studying inflammatory vascular changes.