The involvement of leukocytes in the pathophysiology of DR has mostly examined the role of monocytes and neutrophils with little emphasis on other immune cell types. In this study, we determined the systemic alterations in T cell subsets, myeloid cell types, NK cells, and NKT cells in the streptozotocin (STZ) mouse model of diabetic retinopathy (DR), and the role of NKT cells on retinal leukostasis and permeability changes. C57BL/6 J mice were made diabetic with 60 mg/kg dose of STZ given for 5-days. Flow cytometry assay measured the frequency of leukocyte subsets in the peripheral blood, spleen, and bone marrow of STZ- and vehicle-treated C57BL/6 J mice. Our results showed an increased proportion of memory CD8 T cells and interferon-gamma (IFN-γ) secreting CD8 T cells in the bone marrow of STZ-treated compared to control mice. Subsequently, increased production of inflammatory monocytes in the bone marrow and an enhanced frequency of CD11b + cells in the diabetic retina were seen in STZ-treated compared to control mice. The diabetic mice also exhibited a decrease in total NKT and CD4+NKT cells. A monoclonal antibody-based approach depleted NKT cells from STZ-treated mice, followed by measurements of retinal vascular permeability and leukostasis. The depletion of NKT cells in STZ-treated mice resulted in a significant increase in vascular permeability in the retinal tissue. Together, our results strongly imply the involvement of NKT cells in regulating the pathophysiology of the diabetic retina.

白细胞在 DR 的病理生理学中的参与主要研究了单核细胞和中性粒细胞的作用，很少强调其他免疫细胞类型。在这项研究中，我们确定了糖尿病视网膜病变 (DR) 链脲佐菌素 (STZ) 小鼠模型中 T 细胞亚群、髓样细胞类型、NK 细胞和 NKT 细胞的全身性改变，以及 NKT 细胞对视网膜白细胞淤滞和通透性的作用变化。C57BL/6 J 小鼠用 60 mg/kg 剂量的 STZ 给药 5 天，使其患糖尿病。流式细胞术测定了 STZ 和载体处理的 C57BL/6 J 小鼠的外周血、脾脏和骨髓中白细胞亚群的频率。我们的结果显示，与对照小鼠相比，STZ 治疗的骨髓中记忆 CD8 T 细胞和分泌干扰素-γ（IFN-γ）的 CD8 T 细胞的比例增加。随后，与对照小鼠相比，STZ 治疗的小鼠骨髓中炎症单核细胞的产生增加，糖尿病视网膜中 CD11b + 细胞的频率增加。糖尿病小鼠还表现出总 NKT 和 CD4+NKT 细胞的减少。一种基于单克隆抗体的方法消耗了来自 STZ 治疗小鼠的 NKT 细胞，然后测量视网膜血管通透性和白细胞淤滞。STZ 治疗小鼠中 NKT 细胞的消耗导致视网膜组织中血管通透性的显着增加。总之，我们的结果强烈暗示 NKT 细胞参与调节糖尿病视网膜的病理生理学。糖尿病小鼠还表现出总 NKT 和 CD4+NKT 细胞的减少。一种基于单克隆抗体的方法消耗了来自 STZ 治疗小鼠的 NKT 细胞，然后测量视网膜血管通透性和白细胞淤滞。STZ 治疗小鼠中 NKT 细胞的消耗导致视网膜组织中血管通透性的显着增加。总之，我们的结果强烈暗示 NKT 细胞参与调节糖尿病视网膜的病理生理学。糖尿病小鼠还表现出总 NKT 和 CD4+NKT 细胞的减少。一种基于单克隆抗体的方法消耗了来自 STZ 治疗小鼠的 NKT 细胞，然后测量视网膜血管通透性和白细胞淤滞。STZ 治疗小鼠中 NKT 细胞的消耗导致视网膜组织中血管通透性的显着增加。总之，我们的结果强烈暗示 NKT 细胞参与调节糖尿病视网膜的病理生理学。