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Severe Hypoglycaemia-induced Microglial Inflammation Damages Microvascular Endothelial Cells, Leading to Retinal Destruction

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Publisher Sage Publications
Date 2024 Aug 26
PMID 39187253
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Abstract

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.

References
1.
Valle M, Dworshak J, Sharma A, Ibrahim A, Al-Shabrawey M, Sharma S . Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells. Exp Eye Res. 2018; 178:27-36. PMC: 6361696. DOI: 10.1016/j.exer.2018.09.009. View

2.
Drummond J, Barbosa I, Dantzer R, Teixeira A . The effect of insulin-induced hypoglycemia on inflammatory markers: A systematic review. Brain Behav Immun. 2018; 73:41-50. DOI: 10.1016/j.bbi.2018.05.003. View

3.
Razavi Nematollahi L, Kitabchi A, Kitabchi A, Stentz F, Wan J, Larijani B . Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism. 2009; 58(4):443-8. DOI: 10.1016/j.metabol.2008.10.018. View

4.
Ma L, Wei J, Wan J, Wang W, Wang L, Yuan Y . Low glucose and metformin-induced apoptosis of human ovarian cancer cells is connected to ASK1 via mitochondrial and endoplasmic reticulum stress-associated pathways. J Exp Clin Cancer Res. 2019; 38(1):77. PMC: 6375187. DOI: 10.1186/s13046-019-1090-6. View

5.
Kinuthia U, Wolf A, Langmann T . Microglia and Inflammatory Responses in Diabetic Retinopathy. Front Immunol. 2020; 11:564077. PMC: 7681237. DOI: 10.3389/fimmu.2020.564077. View