Blue-violet light decreases VEGFa production in an in vitro model of AMD.

Mélanie Marie,Coralie Barrau,Serge Picaud,José Sahel,Pauline Gondouin,Thierry Villette,Delphine Pagan

doi:10.1371/journal.pone.0223839

Abstract

Blue light is an identified risk factor for age-related macular degeneration (AMD). The production of vascular endothelial growth factor (VEGF), leading to neovascularization, is a major complication of the wet form of this disease. We investigated how blue light affects VEGF expression and secretion using A2E-loaded retinal pigment epithelium (RPE) cells, a cell model of AMD. Incubation of RPE cells with A2E resulted in a significant increase in VEGF mRNA and, intracellular and secreted VEGF protein levels, but not mRNA levels of VEGFR1 or VEGFR2. Blue light exposure of A2E-loaded RPE cells resulted in a decrease in VEGF mRNA and protein levels, but an increase in VEGFR1 levels. The toxicity of 440 nm light on A2E-loaded RPE cells was enhanced by VEGF supplementation. Our results suggest that age-related A2E accumulation may result in VEGF synthesis and release. This synthesis of VEGF, which enhances blue light toxicity for the RPE cells, is itself suppressed by blue light. Anti-VEGF therapy may therefore improve RPE survival in AMD.

Highlights

Age related macular degeneration (AMD) is characterized by a loss of central high acuity vision [1]
VEGFa mRNA levels increased by two-fold following incubation of retinal pigment epithelium (RPE) cells with A2E, as previously reported by others [26, 48], this increase disappeared by 39 h after the end of A2E incubation (Fig 1A, 1B and 1C)
Our results confirm the A2E-induced potentiation of vascular endothelial growth factor (VEGF) synthesis and release, suggesting that A2E accumulation could stimulate the neovascularization observed in wet AMD

Summary

Introduction

Age related macular degeneration (AMD) is characterized by a loss of central high acuity vision [1]. The dry type of AMD is the most common, accounting for approximately 90% of patients and is characterized by retinal pigment epithelium (RPE) and photoreceptors degeneration over time in the macular area [2]. The wet type affects approximately 10% of patients and is characterized by abnormal blood-vessel growth [2] Such blood-vessel growth is mainly attributed to the release of vascular endothelial growth factor (VEGF), as shown by the success of anti-VEGF therapies [3, 4]. Anti-VEGF therapies have become a major treatment modality in the daily care of wet AMD to suppress the growth of neovessels, which invade the retina from the underlying choroid, located below the retinal pigment epithelium (RPE) [3, 5].

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Discussion

Conclusion