Hydroquinone predisposes for retinal pigment epithelial (RPE) cell degeneration in inflammatory conditions

In addition to hypoxia, inflammation is capable of inducing vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. Excessive levels of VEGF promote choroidal neovascularization and thereby contribute to the pathogenesis of wet age-related macular degeneration (AMD). Intravitreal anti-VEGF injections ameliorate pathological vessel neoformation in wet AMD but excessive dampening of VEGF can result in a degeneration of the RPE. In the present study, we induced VEGF production by exposing human ARPE-19 cells to the pro-inflammatory IL-1 alpha and subsequently to hydroquinone, a component of tobacco smoke that is a major environmental risk factor for AMD. Effects were monitored by measuring the levels of VEGF and anti-angiogenic pigment epithelium-derived factor (PEDF) using an enzyme-linked immunosorbent assay (ELISA) technique. In addition, we measured the production of reactive oxygen species (ROS) using the 2',7'-dichlorofluorescin diacetate (H2DCFDA) probe and studied the effects of two anti-oxidants, ammonium pyrrolidinedithiocarbamate (APDC) and N-acetyl-cysteine (NAC), on VEGF production. Cellular and secreted VEGF as well as secreted PEDF levels were reduced at all tested hydroquinone concentrations (10, 50, or 200 mu M); these effects were evident prior to any reduction of cell viability evoked by hydroquinone. Cell viability was carefully explored in our previous study and verified by microscoping in the present study. APDC further reduced the VEGF levels, whereas NAC increased them. The 50 mu M concentration of hydroquinone increased ROS production in ARPE-19 cells primed with IL-1 alpha. Hydroquinone disturbs the regulatory balance of VEGF and PEDF in inflammatory conditions. These data support the idea that hydroquinone mediates RPE degeneration by reducing VEGF levels and may predispose to dry AMD since VEGF is as well important for retinal integrity.

Automated summary

In addition to hypoxia, inflammation can also induce the expression of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. Excessive VEGF promotes choroidal neovascularization, contributing to the pathogenesis of wet age-related macular degeneration (AMD). However, excessive dampening of VEGF can lead to RPE degeneration. This study found that hydroquinone, a component of tobacco smoke and a major environmental risk factor for AMD, reduces VEGF levels in inflammatory conditions and may predispose to dry AMD.