Macrophage Lab, Department of Microbiology and ImmunologyInstitute of Endemic Disease, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pediatric Ophthalmology, Seoul National University Hospital, Seoul, Republic of Korea.
Sci Rep. 2024 Sep 30;14(1):22664. doi: 10.1038/s41598-024-72166-9.
Diabetic retinopathy (DR) is a prevalent complication of diabetes, often resulting in vision loss and blindness. Existing treatments primarily aim to control blood sugar levels and inhibit angiogenesis. However, current therapies for DR, such as anti-VEGF and laser photocoagulation, are frequently invasive, and can cause adverse side effects. Consequently, there is a critical need for new preventive therapeutics to address DR more effectively. This study aimed to examine the therapeutic potential of a histamine H receptor (HRH4) antagonist as a preventive treatment for DR in mice. A mouse model of DR was established by intraperitoneally injecting 200 mg/kg of streptozotocin (STZ). Immune cell infiltration into the retina of mice with STZ-induced diabetes was measured using fluorescence-activated cell sorting (FACS) 12 weeks after STZ injection. The preventive effects of the HRH4 antagonist on inflammation and pathological retinal vessel leakage were determined in a mouse model of DR. Infiltration of HRH4-expressing macrophages increased in the retina of mice with STZ-induced DR. The HRH4 antagonist prevented macrophage infiltration and retinal vascular leakage to prevent STZ-induced DR in mice without causing any retinal toxicity. The infiltration of macrophages increased in the retina of mice with STZ-induced diabetes through HRH4, indicating that HRH4 is potentially a novel preventative therapeutic target in DR. These findings suggest that targeting HRH4 is a promising strategy for the prevention and treatment of DR.
糖尿病性视网膜病变（DR）是糖尿病的一种常见并发症，常导致视力丧失和失明。现有的治疗方法主要旨在控制血糖水平和抑制血管生成。然而，DR 的现有治疗方法，如抗 VEGF 和激光光凝，通常具有侵入性，并且可能引起不良反应。因此，迫切需要新的预防疗法来更有效地治疗 DR。本研究旨在研究组胺 H 受体（HRH4）拮抗剂作为 DR 预防治疗在小鼠中的治疗潜力。通过腹腔注射 200mg/kg 的链脲佐菌素（STZ）建立 DR 小鼠模型。在 STZ 注射 12 周后，使用荧光激活细胞分选（FACS）测量 STZ 诱导的糖尿病小鼠视网膜中免疫细胞的浸润。在 DR 小鼠模型中，确定 HRH4 拮抗剂对炎症和病理性视网膜血管渗漏的预防作用。在 STZ 诱导的 DR 小鼠的视网膜中，表达 HRH4 的巨噬细胞浸润增加。HRH4 拮抗剂可预防巨噬细胞浸润和视网膜血管渗漏，从而预防 STZ 诱导的 DR，而不会引起任何视网膜毒性。HRH4 通过 HRH4 增加了 STZ 诱导的糖尿病小鼠的视网膜中巨噬细胞的浸润，这表明 HRH4 可能是 DR 的一种新的预防治疗靶标。这些发现表明，靶向 HRH4 是预防和治疗 DR 的一种有前途的策略。
