Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.
Essilor International R&D, Charenton-le-Pont, France.
PLoS One. 2019 Oct 23;14(10):e0223839. doi: 10.1371/journal.pone.0223839. eCollection 2019.
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.
蓝光是与年龄相关的黄斑变性（AMD）有关的一个确定的风险因素。血管内皮生长因子（VEGF）的产生导致新生血管形成，是这种疾病湿性形式的主要并发症。我们研究了蓝光如何影响载有 A2E 的视网膜色素上皮（RPE）细胞中 VEGF 的表达和分泌，A2E 载有 RPE 细胞是 AMD 的细胞模型。用 A2E 孵育 RPE 细胞会导致 VEGF mRNA 以及细胞内和分泌的 VEGF 蛋白水平显著增加，但 VEGFR1 或 VEGFR2 的 mRNA 水平没有增加。蓝光照射载有 A2E 的 RPE 细胞会导致 VEGF mRNA 和蛋白水平降低，但 VEGFR1 水平升高。VEGF 的补充增强了 440nm 光对载有 A2E 的 RPE 细胞的毒性。我们的结果表明，与年龄相关的 A2E 积累可能导致 VEGF 的合成和释放。这种 VEGF 的合成增强了蓝光对 RPE 细胞的毒性，而蓝光本身又抑制了 VEGF 的合成。因此，抗 VEGF 治疗可能会改善 AMD 中 RPE 的存活。
