Leukotrienes regulate vascular endothelial cell growth factor in retinal cells

Abstract

Purpose : One of the most targeted molecules in the treatment of diabetic retinopathy is the angiogenic molecule, vascular endothelial cell growth factor (VEGF). In the current study, we investigated the role of leukotrienes and leukotriene inhibition on the regulation of VEGF generation and secretion in mouse retinal cells.

Methods : Mouse retinal astrocytes were grown in physiologic (5.5 mM) or high-glucose media (30 mM) for 5 days. Cells were treated with Leukotriene B₄ (LTB₄) or leukotriene C₄ (LTC₄) overnight in 1% FBS media. Montelukast was added 20 minutes prior to leukotriene treatment. VEGF secretion in cell culture media was assessed by ELISA and VEGF expression in cell lysate was measured by Western blotting.

Results : When compared to cells grown in physiologic glucose, cells grown in high glucose synthesized elevated (1.4-fold increase) VEGF levels within the cells (p=0.0001) and secreted more VEGF levels (p=0.0286) into the media. Addition of LTB₄ further increased VEGF level (p=0.0080) in retinal astrocytes. Pretreatment of astrocytes with montelukast nullified LTB₄meditaed VEGF expression completely (p=0.0002). Similar to LTB₄, LTC₄ [RG1] also caused increase in VEGF synthesis (p=0.006) and secretion (p=0.05) in mouse retinal astrocytes.

Conclusions : Leukotrienes regulate synthesis and secretion of angiogenic factor, VEGF and leukotriene antagonism may slow down the development of diabetic retinopathy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.