Age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR) are two of the most common and severe causes of vision loss in the population. Both conditions are associated with excessive levels of vascular endothelial growth factor (VEGF) in the eye which results in an increase in the formation of new blood vessels through a process called neovascularisation. As such, anti-VEGF therapies are currently utilised as a treatment for patients with AMD however they are associated with painful administration of injections and potential degeneration of healthy endothelium. There is therefore growing interest in alternate treatment options to reduce neovascularisation in the eye. The use of carotenoids, lutein (L) and zeaxanthin (Z), has been shown to improve vision loss parameters in patients with AMD, however the underlying mechanisms are not well-understood. We studied the impact of these compounds on neovascularisation processes using an in vitro cell model of the retinal microvascular endothelium. Our findings show that L and Z reduced VEGF-induced tube formation whilst, in combination (5:1 ratio), the compounds significantly blocked VEGF-induced neovascularisation. The carotenoids, individually and in combination, reduced VEGF-induced oxidative stress concomitant with increased activity of the NADPH oxidase, Nox4. We further demonstrated that the Nox4 inhibitor, GLX7013114, attenuated the protective effect of L and Z. Taken together, these findings indicate the protective effect of the carotenoids, L and Z, in reducing VEGF-mediated neovascularisation via a Nox4-dependent pathway. These studies implicate the potential for these compounds to be used as a therapeutic approach for patients suffering from AMD and proliferative DR.

年龄相关性黄斑变性（AMD）和增生性糖尿病性视网膜病变（DR）是人群中视力丧失最常见和最严重的两种原因。两种情况都与眼睛中血管内皮生长因子（VEGF）的水平过高有关，这会通过称为新血管形成的过程导致新血管形成的增加。因此，抗VEGF疗法目前被用作AMD患者的疗法，但是它们与注射的痛苦给药和健康的内皮的潜在变性有关。因此，对于减少眼睛新血管形成的替代治疗选择的兴趣日益浓厚。已显示使用类胡萝卜素，叶黄素（L）和玉米黄质（Z）可改善AMD患者的视力丧失参数，但是，其潜在的机制还不为人所理解。我们使用一种药物研究了这些化合物对新血管形成过程的影响。视网膜微血管内皮细胞的体外细胞模型。我们的发现表明，L和Z减少了VEGF诱导的管形成，而组合使用（5：1的比例），这些化合物显着阻断了VEGF诱导的新血管形成。类胡萝卜素单独或组合可减少VEGF诱导的氧化应激，同时增加NADPH氧化酶Nox4的活性。我们进一步证明了Nox4抑制剂GLX7013114减弱了L和Z的保护作用。总而言之，这些发现表明类胡萝卜素L和Z通过Nox4依赖性途径减少VEGF介导的新血管形成的保护作用。这些研究表明将这些化合物用作患有AMD和增生性DR的患者的治疗方法的潜力。