Abstract
The pathological superoxidative condition that retinal pigment epithelium (RPE) cells experience contributed to the advancement of age-related macular degeneration (AMD), which was accompanied by significant neovascularization. Therefore, the discovery of novel pharmacological candidates to ameliorate oxidative damage (H2O2) against RPE cells and inhibit the following angiogenesis simultaneously is urgently needed. Herein, we found that kinsenoside (Kin), an active component derived from Anoectochilus roxburghii, was able to protect RPE cells effectively and attenuate subsequent angiogenesis. In this study, H2O2-induced oxidative injury reduced RPE cell viability and increased cell apoptosis, which was significantly rescued by the treatment with Kin. Compared with H2O2 alone, Kin decreased the levels of Bax and increased the production of Bcl-2 in RPE cells. H2O2-stimulated VEGF up-regulation was inhibited by Kin treatment. Human umbilical vein endothelial cell (HUVEC) neovascularization induced by conditioned medium (CM) from H2O2-stimulated RPE cells was attenuated by treatment with Kin, VEGF antagonist, NF-κB, Erk-MAPK, and p38-MAPK inhibitors. Additionally, H2O2-activated phosphorylated expression of IκBα, p65, Erk, and p38 in RPE cells was inhibited by treatment with Kin. Taken together, Kin protected RPE from apoptosis against oxidative stress while simultaneously decreasing apoptosis-related neovascularization. This could be ascribed to the inhibition of Erk/p38/NF-κB signaling by Kin that contributed to the resulting decreased VEGF expression in H2O2-treated RPE cells.
Highlights
Age-related macular degeneration is the leading cause of irreversible visual disability among the elderly population, characterized by the accumulation of drusen between Bruch’s membrane in macular and retinal pigment epithelium (RPE) in the early stage and interconvertible “wet” and “dry” patterns in the late stage (Jager et al, 2008)
In order to induce significant H2O2-triggered RPE apoptosis for age-related macular degeneration (AMD) modeling, 100 μM of H2O2 was deployed for further experiments
For B cell lymphoma-2 (Bcl-2) protein expression, the Vehicle group showed a significant decrease, whereas both low and high Kin reversed this attenuation. These results indicated that the protective ability of Kin against H2O2-induced RPE apoptosis was partly attributed to the regulation of the Bcl-2 associated X protein (Bax)/Bcl-2 ratio, implicating the possible modulation of the mitochondrial-dependent cell death pathway (Wang et al, 2017) by Kin in H2O2-treated RPE cells
Summary
Age-related macular degeneration is the leading cause of irreversible visual disability among the elderly population, characterized by the accumulation of drusen between Bruch’s membrane in macular and RPE in the early stage and interconvertible “wet” and “dry” patterns in the late stage (Jager et al, 2008). By protecting the retina from excess light and maintaining photoreceptor survival, RPE cells are capable of modulating sub-retinal ion balance and promoting the clearance of photoreceptor outer segments (POSs) (Kevany and Palczewski, 2010). They do not renew after differentiation (Ebrahimi et al, 2017), inevitably resulting in RPE apoptosis caused by long-term oxidative damage. In severe AMD cases, these apoptotic RPE cells release VEGF, the most significant pro-angiogenic factor, resulting in the activation of CNV and the further development of wet AMD (Dinc et al, 2017). There is an urgent need for the development of novel anti-AMD therapeutic strategies that simultaneously protect RPE cells and inhibit the following neovascularization
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
