Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.
Department of Immunology, Cleveland Clinic, Cleveland, OH, 44106, USA.
Prog Retin Eye Res. 2021 Sep;84:100940. doi: 10.1016/j.preteyeres.2021.100940. Epub 2021 Jan 8.
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.
在过去的半个世纪中，糖尿病的患病率一直在稳步上升，随之而来的是其相关并发症的负担，包括糖尿病性视网膜病变（DR）。DR 目前是美国工作年龄段成年人视力丧失的最常见原因。从历史上看，DR 的诊断和分类是基于眼底镜检查可见的血管改变来进行的。然而，最近的技术进步已经证实了神经视网膜的病理学变化，而这些变化在任何可检测到的血管变化之前就已经发生了。这些变化，加上分子研究，以及抗炎治疗在 DR 患者中的积极影响，突显了固有免疫系统的核心作用。与糖尿病的全身性影响类似，免疫失调已被越来越多地确定为 DR 病理生理学的关键因素，因为它干扰了正常的体内平衡系统。这篇综述利用各种模型系统中不断增加的文献，证明了免疫系统的所有三个支柱（免疫活性细胞、介质和补体系统）都明显参与其中。它还表明，这些因素中的每一个的相对贡献都需要更广泛的分析，包括在疾病进展的连续过程中对人类组织进行分析。最后，尽管这篇综述表明，免疫系统的复杂相互作用提出的问题多于答案，但免疫系统的三个支柱之间的密切联系也可能指向可能的新靶点，以逆转甚至阻止 DR 的进展。
