Abstract
Purpose: Diabetic retinopathy is marked by hyperglycemia-induced inflammation and chemokine signaling that drive immune cell infiltration and retinal damage. As bevacizumab offers limited benefit in some cases, targeting broader inflammatory pathways with agents like triamcinolone may enhance therapeutic outcomes.
Methods: ARPE-19 cells exposed to hyperglycemic conditions (30 mM glucose) for 72 hours were treated with bevacizumab (0.3 mg/ml), triamcinolone (1mg/ml), or their combination. Cell proliferation was assessed using the MTT assay, while ELISA measured VEGF, MCP- 1, and CXCL10 secretion, and qRT-PCR analyzed CCR2 and CXCR3 gene expression. Three independent biological replicates were used in each experiment.
Results: Hyperglycemia markedly increased cell proliferation after 24 and 48 hours (P < 0.001). Bevacizumab or triamcinolone alone did not alter cell proliferation under hyperglycemic stress; however, their combined treatment significantly reduced proliferation (P < 0.001). Hyperglycemia markedly elevated VEGF secretion (P < 0.001), whereas bevacizumab, triamcinolone, and especially their combination significantly suppressed it (all P < 0.05). All three treatment conditions significantly reduced MCP-1 levels (P < 0.05), while only the combined therapy lowered CXCL10 secretion (P < 0.01). Regarding chemokine receptors, both drugs individually downregulated CCR2 and CXCR3 expression, with the combination producing an additive inhibitory effect (CCR2: P < 0.001; CXCR3: P < 0.05).
Conclusion: These results reveal that triamcinolone may complement bevacizumab by targeting VEGF-independent inflammatory pathways, providing mechanistic insight into combination therapy for diabetic macular edema (DME), particularly in patients with persistent DME despite anti-VEGF monotherapy.