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Carla Jhoana J Ramos; Stimulation of retinal glia cells by palmitic acid. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2727.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) has been traditionally diagnosed as retinal microvascular alterations that result in vascular leakage and growth of new blood vessels in advanced stages of DR. The retinal microvasculature is intimately associated with neurons and glia cells. Recent evidence shows that these cells are affected by DR prior to clinically detectable vascular lesions, suggesting that these cells play critical roles in DR pathophysiology. Retinal glia cells, comprised of Müller cells, astrocytes, and microglia, serve to maintain retinal homeostasis. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia accompanied by dyslipidemia and hypertension. Previous work in our laboratory has demonstrated that palmitic acid (PA) stimulates retinal Müller cells to upregulate inflammatory gene targets. The purpose of this project is to understand how insults designed to mimic hyperglycemia, dyslipidemia and hypertension affect retinal glia and compare their cell-specific responses.
Primary human retinal Müller cells and retinal astrocytes were used for RNA-sequencing. Hyperglycemia, dyslipidemia and hypertension were modeled using D-glucose (30mM), palmitic acid (250µM), and angiotensin 2 (1µM), respectively. Total RNA was isolated and submitted to core facilities at Vanderbilt University, where RNA-sequencing and analyses were performed.
Both glucose and angiotensin 2 caused little to no expression differences in either glial cell type compared to control conditions. By contrast, PA stimulated both astrocytes and Müller cells, resulting in 2846 and 2706 differentially expressed genes, respectively. Interestingly, both astrocytes and Müller cells showed significant upregulation in the following C-X-C family chemokines: CXCL2 by 92-and 87-fold in astrocytes and Müller cells, respectively; CXCL3 by 32- and 73-fold; and CXCL8 by 18- and 66-fold, respectively (p<0.05). Other interesting genes significantly upregulated in both cell types were IL6, IL1A, and PTGS2 (p<0.05).
Both glia cell types demonstrated profound expression changes, particularly related to inflammatory signaling, in response to conditions designed to mimic dyslipidemia. Collectively, these data suggest that an understanding of non-glucose-driven pathologies may be important for the development of early detection and intervention strategies against DR progression. Further testing will extend these results to include microglia.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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