期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-23601-1
关键词
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资金
- National Institutes of Health [R01-EY07533, R01-EY023639, P30-EY008126, P30-DK020593, T32-EY07135]
- National Center for Advancing Translational Sciences [2UL1-TR000445]
- Research to Prevent Blindness, Inc.
- Carl Marshall Reeves & Mildred Almen Reeves Foundation, Inc.
Chronic hyperglycemia is thought to be the major stimulator of retinal dysfunction in diabetic retinopathy (DR). Thus, many diabetes-related systemic factors have been overlooked as inducers of DR pathology. Cell culture models of retinal cell types are frequently used to mechanistically study DR, but appropriate stimulators of DR-like factors are difficult to identify. Furthermore, elevated glucose, a gold standard for cell culture treatments, yields little to no response from many primary human retinal cells. Thus, the goal of this project was to demonstrate the effectiveness of the free fatty acid, palmitic acid and compare its use alone and in combination with elevated glucose as a stimulus for human Muller cells, a retinal glial cell type that is activated early in DR pathogenesis and uniquely responsive to fatty acids. Using RNA sequencing, we identified a variety of DR-relevant pathways, including NF kappa B signaling and inflammation, intracellular lipid signaling, angiogenesis, and MAPK signaling, that were stimulated by palmitic acid, while elevated glucose alone did not significantly alter any diabetes-relevant pathways. Co-treatment of high glucose with palmitic acid potentiated the expression of several DR-relevant angiogenic and inflammatory targets, including PTGS2 (COX-2) and CXCL8 (IL-8).
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