## 1 Introduction  
Resveratrol(3,4',5-trihydroxystilbene-RSV) is a biologically active compound from the phytoalexin family. This phenolic substance exists in isomeric cis- and trans-form, wherein trans-form is more stable in the biological systems [1]. RSV is synthesised by many plant species, such as grape wine (Vitis vinifera), berries, peanuts, and medicinal plants [2]. It is also present in plant-derived products, including wine, which is the common source of RSV in the Western European diet [3]. This compound is well characterised in terms of its antioxidant properties as a scavenger of the reactive oxygen species (ROS) [4]. RSV has various medical applications. The main biological role of RSV is associated with its positive effect on the cardiovascular system. RSV reduces inflammation and apoptosis in vascular endothelium, increases the flexibility of the aorta, decreases the level of cholesterol and triglycerides in the blood, protects most organs (kidneys, heart and brain) from ischemic injury, and may reduce the risk of heart attack [5]. It also normalises the concentration of glucose in diet-induced obese and diabetic mice suggesting a similar eventual effect in humans [6]. RSV significantly exhibits anti-inflammatory and anti-angiogenic activities and regulates many cellular signaling pathways associated with cell metabolism, proliferation, differentiation, migration, and invasiveness of normal and cancer cells [7]. It also affects the in vitro and in vivo formation of new vessels [8]. Currently, RSV is widely studied as a potential antitumor therapeutic, in which its antigenicity-related and anti-proliferative activities take part [4]. In vitro studies showed that RSV significantly decreases the proliferation of many types of cancer cells including pancreatic cancer [9], breast cancer [10], and colon cancer [11]. Similarly, in vivo RSV could modulate tumorigenesis, affecting angiogenesis, growth, and development of tumors [8]. Next to anticancer therapy, the anti-angiogenic activity of RSV may potentially be used to inhibit pathologic neovascularization in age-related eye diseases such as age-related macular degeneration (AMD) or diabetic retinopathy; the main diseases responsible for vision loss in the 65 and older age population. AMD is recognised as a chronic and progressive degeneration of the macula, resulting in loss of central vision in the elderly [12], significantly deteriorating the quality of life and increasing depression levels compared to without AMD elderly [13]. This disorder is marked by the presence of drusen in the macula followed by geographic atrophy or choroidal neovascularization (CNV) [12] and classified in terms of expected invasion side into the retina. Because the development of neovascularization is strictly correlated with vascular endothelial growth factor (VEGF), an anti-VEGF therapy has found its place in AMD treatment and it is considered to be a current gold standard therapy [14]. Targeted immunotherapy against VEGF is currently used in AMD treatments, and some new VEGF inhibitors are in clinical trials [15]. However, some authors revealed that a long-term incubation with anti-VEGF agents may induce epithelial to mesenchymal transition in ARPE-19 cells, which provides a novel insight into the pathogenesis of intravitreal anti-VEGF-associated complications [16]. Taking into account the anti-angiogenic activities of RSV, it may decrease the VEGF expression leading to inhibition of neovascularization development and therefore affecting pathological angiogenesis. [PERSON] et al. demonstrated that RSV inhibits the hypoxia-induced VEGF in ARPE-19 cells by CXCR expression suppression through decreased NF-\(\kappa\)B phosphorylation [17]. [PERSON] et al. showed that RSV may reverse the adverse effects of anti-VEGF therapy as bevacizumab on cultured ARPE-19 cells. Epithelial to mesenchymal transition was reported to be lower in combination agents (bevacizumab + RSV) treated cultures compared to bevacizumab-only treated cultures.