Gettinger Kate, Lee Deokho, Negishi Kazuno, Kurihara Toshihide
Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Int J Mol Sci. 2025 May 5;26(9):4385. doi: 10.3390/ijms26094385.
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 , , , , and in the STZ UCCAO group compared to other groups. Our model can serve as an accelerated DR model for studying inflammatory vascular changes.
糖尿病视网膜病变（DR）是导致视力损害的主要原因。为了更好地理解其病理，需要临床相关的实验模型。广泛使用的DR模型（尤其是链脲佐菌素（STZ）诱导的模型）需要较长时间才能达到DR表型终点，并且缺乏缺血表型，这与人类情况不同。单侧颈总动脉闭塞（UCCAO）可造成视网膜缺血损伤。我们探究了UCCAO在STZ诱导的小鼠中的病理协同作用。将STZ（90 mg/kg）腹腔注射到成年C57BL/6小鼠体内，持续三天。四周后，进行右侧UCCAO手术。UCCAO术后一周，用异凝集素B4对视网膜样本进行染色，以分析细胞和血管变化。在UCCAO术后一天和一周获取视网膜样本，并进行定量PCR（qPCR）以观察炎症和缺血反应。只有STZ+UCCAO组的炎症细胞增多。与其他组相比，STZ+UCCAO视网膜在毛细血管和大血管大小方面存在显著差异。与其他组相比，在术后一天和一周时，STZ+UCCAO组中炎症基因、、、、和的mRNA表达发生了变化。我们的模型可作为研究炎症性血管变化的加速DR模型。
