Statins decreases vascular epithelial growth factor (VEGF) expression in experimental age-related macular degradation (AMD) model by down-regulation of receptor for advanced glycation end-products (RAGE)

Abstract

Purpose : Statins (atorvastatin and lovastatin etc.), cholesterol lowing medications, are inhibitors for 3-hydroxy-3-methylglutaryl coenzyme A reductase, and are recently reported to be useful for decreasing the risk of wet-type age-related macular degeneration (AMD). However, the molecular mechanisms how statins reduce the risk of AMD remains unclear. In this study, we examined the effects of statins on the expression of vascular endothelial growth factor (VEGF) and receptor for advanced glycation end-products (AGE) (RAGE) in retinal pigment epithelial (RPE) cells.

Methods : h1RPE7, human RPE cells, damaged by 20 µM hydroquinone (HQ)+300 µg/mL AGE, were treated with atorvastatin (100 nM) or lovastatin (2 µM) for 24 hours. After the treatment, the expression of VEGF and RAGE was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). VEGF, secreted in the culture medium, was measured by enzyme-linked immunosorbent assay. To know the impact of RAGE in VEGF expression, small interfering RNA (siRNA) for RAGE (siRAGE) was introduced into h1RPE7 cells by lipofection method and VEGF expression was measured by real-time RT-PCR.

Results : Real-time RT-PCR revealed that the mRNA levels of VEGF and RAGE in h1RPE7 cells were increased by HQ+AGE (P=0.0026 and P=0.03, respectively). The level of VEGF in the culture medium was concomittently elevated (P<0.001). Both the addition of atorvastatin and lovastatin attenuated the HQ+AGE-induced VEGF and RAGE expression (P<0.002 and P<0.03, respectively). The addition of atorvastatin and lovastatin also decreased VEGF levels in HQ+AGE treated cell culture medium (P= 0.02). RNA interference of RAGE attenuated the up-regulation of VEGF in the HQ+AGE treated cells (P< 0.05).

Conclusions : Statins attenuated the HQ+AGE-induced VEGF expression via decreasing RAGE expression. As VEGF is an important factor for developing wet AMD. Statins could decrease the risk of wet-type AMD and be a preventive medicine.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.