Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
GROW Laboratory, Narayana Nethralaya Foundation, Bengaluru, India.
JCI Insight. 2023 Jun 22;8(12):e168945. doi: 10.1172/jci.insight.168945.
Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING has been previously shown to regulate cell senescence and inflammation, key contributors to the development and progression of DR. To investigate the mechanism whereby STING contributes to the pathogenesis of DR, diabetes was induced in STING-KO mice and STINGGT (loss-of-function mutation) mice, and molecular alterations and pathological changes in the retina were characterized. We report that retinal endothelial cell senescence, inflammation, and capillary degeneration were all inhibited in STING-KO diabetic mice; these observations were independently corroborated in STINGGT mice. These protective effects resulted from the reduction in TBK1, IRF3, and NF-κB phosphorylation in the absence of STING. Collectively, our results suggest that targeting STING may be an effective therapy for the early prevention and treatment of DR.
糖尿病性视网膜病变（DR）是导致工作年龄成年人失明的主要原因，仍然是全球重要的公共卫生问题。在这里，我们证明了干扰素基因刺激物（STING）的表达在 DR 患者和糖尿病眼病动物模型中增加。STING 先前已被证明可调节细胞衰老和炎症，这是 DR 发展和进展的关键因素。为了研究 STING 促进 DR 发病机制的机制，在 STING-KO 小鼠和 STINGGT（功能丧失突变）小鼠中诱导糖尿病，并对视网膜中的分子变化和病理变化进行了表征。我们报告说，视网膜内皮细胞衰老、炎症和毛细血管退化在 STING-KO 糖尿病小鼠中均受到抑制；在 STINGGT 小鼠中也独立地证实了这些观察结果。这些保护作用是由于缺乏 STING 导致 TBK1、IRF3 和 NF-κB 磷酸化减少所致。总之，我们的结果表明，靶向 STING 可能是预防和治疗 DR 的有效方法。
