The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.

在过去的半个世纪里，糖尿病的患病率一直在稳步上升，同时伴随着包括糖尿病视网膜病变 (DR) 在内的相关并发症的负担。DR 目前是美国工作年龄成年人视力丧失的最常见原因。从历史上看，DR 是根据眼底镜检查可见的内容进行临床诊断和分类的。那就是脉管系统的改变。然而，最近的技术进步已经在任何可检测到的血管变化之前证实了神经视网膜的病理学。这些，加上分子研究，以及抗炎治疗对 DR 患者的积极影响，突出了先天免疫系统的核心参与。让人想起糖尿病的全身影响，通过干扰正常的稳态系统，免疫失调已越来越多地被确定为 DR 病理生理学的关键因素。这篇综述使用越来越多的跨各种模型系统的文献来证明免疫系统的所有三个支柱的明确参与：免疫活性细胞、介质和补体系统。它还证明了这些中每一个的相对贡献如何需要更广泛的分析，包括在疾病进展的连续体中的人体组织中。最后，虽然这篇综述展示了免疫系统的复杂相互作用如何提出的问题多于答案，但免疫系统三大支柱的密切联系性质也可能指出可能的新目标来逆转甚至阻止逆向性视网膜病变。