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 Müller 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 NFκB 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).