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Inflammatory Mediators Induce VEGF‐A and VEGF‐C secretion by Human Retinal Cells

Vascular endothelial growth factors (VEGF) are the primary causative agents involved in retinal and choroidal neovascularization that may lead to blinding retinal diseases. There is increasing evidence suggesting a role for inflammatory processes in retinal diseases of angiogenic etiology. We used primary cultures of human retinal pigment epithelial cells (HRPE) to evaluate the effect of inflammatory mediators on VEGF expression. HRPE cultures were incubated in serum‐free medium for 24 hr in the presence of inflammatory mediators (IM), IFN‐γ, TNF‐α or IL‐1 and various combinations of these cytokines. The secretion of VEGF‐A and VEGF‐C by HRPE were significantly increased in response to IFN‐γ, TNF‐α and IL‐1. The secretion of VEGF‐B, VEGF‐D, and angiopoitin‐1 and ‐2 were not observed in control and IM treated HRPE. VEGF‐A secretion by control and IM treated HRPE were 57 and 823 pg/ml (n=4) respectively. VEGF‐C secretion by control and IM treated HRPE were 221 and 3574 pg/ml (n=4) respectively. The secretion of VEGF‐A and VEGF‐C was enhanced by IFN‐γ, TNF‐α and IL‐1 individuallly and cumulatively. RT‐PCR analysis showed significant elevation of VEGF‐A and VEGF‐C mRNA levels in HRPE treated with IM. Augumented secretion of VEGF‐A and VEGF‐C by HRPE under the influence of IM may affect retinal and choroidal vasculature leading to retinal and choroidal neovascularization.