Homme Rubens P, Singh Mahavir, Majumder Avisek, George Akash K, Nair Kavya, Sandhu Harpal S, Tyagi Neetu, Lominadze David, Tyagi Suresh C
Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States.
Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States.
Front Physiol. 2018 Sep 5;9:1268. doi: 10.3389/fphys.2018.01268. eCollection 2018.
Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells' redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects.
糖尿病患者除了存在糖代谢异常外，还患有一系列生理异常。这些异常通常通过调节多个炎症相关基因、其各自的基因产物、同型半胱氨酸代谢和细胞焦亡，导致全身炎症。这种稳态破坏的本质通过上调免疫反应、增强视网膜新生血管形成、上调表观遗传事件以及扰乱细胞的氧化还原调节系统，重新设定了糖尿病患者的整体生理状态。这种改变的病理生理环境可导致糖尿病视网膜病变（DR）的发生，这是一种具有微血管并发症的、威胁视力的衰弱性眼病。DR是全世界工作年龄成年人不可逆失明的最常见原因，因为它可导致视网膜严重的结构和功能重塑，降低视力，从而降低生活质量。在本手稿中，我们试图总结近期的进展和新见解，以探索免疫系统各组成部分与其代谢调控之间这种相互交织的串扰的本质，从而阐明DR的病理生理学。了解参与DR的细胞和分子因素的多方面性质，可能揭示有效诊断、治疗、预后、预防工具的新靶点，并最终揭示对抗易感人群中DR发生和发展的策略。
