## 3 Discussion  
The increase in the human lifespan causes a rapid increase in age-related eye diseases, such as retinal vein occlusions, age-related macular degeneration, and retinopathy of prematurity (ROP) [24]. It is predicted that in 2040, there will be 14.9-21.5 million individuals in Europe with early AMD and 3.9-4.8 million with late one [25]. It is known that in all these eye-related diseases, pathological angiogenesis is the main culprit. Angiogenesis is a physiological process in which endothelial cells over-proliferate and forms new blood vessels. The critical factors in the initiation and development of the angiogenesis process are proangiogenic cytokines, such as VEGF. Blocking VEGF by anti-VEGF is one of the therapeutic strategies for the prevention of pathological angiogenesis. However, the administration of anti-VEGF does not fully inhibit the process of pathological angiogenesis due to the increase in the expression of other angiogenic factors in the eye (e.g., bFGF) [26]. Figure 5: Secretion of angiogenic cytokines by the RSV treated HECa10 and ARPE-19 cells. VEGF and bFGF concentration in the supernatants from (**A,B**) HECa10 and (**C,D**) ARPE-19 cell lines cultures after 24 h treatment with RSV at 1, 5, 10, 50, and 100 \(\upmu\)M were measured using ELISA test. Control cells were cultured with 0.1% DMSO and without RSV. The results are presented as mean \(\pm\) SD in at least three experiments with \({}^{*}p<\) 0.05, \({}^{**}p<\) 0.01, \({}^{**}p<\) 0.001, \({}^{***}p<\) 0.0001 compared to the control. Therefore, there is a need for novel therapeutics which will not only attenuate or inhibit the angiogenesis process but will also be able to operate through different or complementary mechanisms. One such compound is RSV. It affects endothelial cell proliferation and migration capacity, which we demonstrated previously [21]. Here, we assess the in vitro study effect of RSV on two different cells found in the eye structure: endothelial cells (involved in neoangiogenesis in the eye) and retinal pigment epithelial (damage of the cells caused AMD) cells. We want to check if the effect of RSV is the effect induced by RSV is selective and if it has the same effect on both types of cells. It is well documented that RSV causes a decrease in proliferation and induces apoptosis in numerous cancer cell lines, such as human prostate carcinoma LNCaP cells, human breast cancer cells, mouse JB6 epidermal cell line, and HL60 human leukemia cell line [27; 28; 29; 30]. The antitumor concentration of RSV ranges from 10 to 300 uM and the degree of its action is time and cell-type dependent [31; 32]. Here, the obtained results point out that the RSV in high concentrations (50 and 100 uM) was affecting the growth of endothelial cells but not retinal pigment. The cause by which RSV induces endothelial cell death was apoptosis. In contrast to the HECa10 cells, RSV at 1-100 uM concentration did not affect apoptosis and necrosis of the ARPE-19 cells. Taken together, RSV at 50 and 100 uM concentrations promoted endothelial cells elimination by apoptosis while did not affect the retinal pigment epithelial cells. The effect of RSV on endothelial cells is in agreement with our previous study [21] and others. [PERSON] et al. (2010) observed a decrease in endothelial cell viability (by apoptosis) after RSV treatment (50 uM, 48 h) when the cell was co-cultured with A375, YUZZA6, or WM3211 melanoma cells [33]. [PERSON] and [PERSON] in 2017 reviewed the effect of RSV on endometriosis and found that the polyphenol not only decreased the proliferation of endometrial cells (through apoptosis induction) but also affected endothelial cells (decreased proliferating activity associated with decreased VEGF level) [34]. Contrarily, some studies indicate that RSV may reveal proangiogenic properties in other cell lines.