Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction

• Published in: Diabetes & vascular disease research 2024-07, Vol.21 (4), p.14791641241278506
• Main Authors: Hu, Yuxin, Li, Zhen, Li, Hongxue, Xu, Qian, Xu, Chengye, Lin, Wenjian, Ma, Xuefei, Hao, Ming, Kuang, Hongyu
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Blood-Retinal Barrier - metabolism; Blood-Retinal Barrier - pathology; Capillary Permeability; Cell Line; Claudin-1 - genetics; Claudin-1 - metabolism; Cytokines - metabolism; Disease Models, Animal; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelial Cells - ultrastructure; Humans; Hypoglycemia - metabolism; Hypoglycemia - pathology; Inflammation Mediators - metabolism; Male; Mice, Inbred C57BL; Microglia - metabolism; Microglia - pathology; Microvessels - metabolism; Microvessels - pathology; Occludin - metabolism; Original; Retinal Vessels - metabolism; Retinal Vessels - pathology; Signal Transduction; Tight Junctions - metabolism; Tight Junctions - pathology; Tight Junctions - ultrastructure
• ISSN: 1479-1641; 1752-8984; 1752-8984
• DOI: 10.1177/14791641241278506

Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1β, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.