Induction of Oxidative Stress on Retinal Pigment Epithelial Cells Triggered a Proangiogenic Environment

Dry age-related macular degeneration (AMD) can progress to wet AMD when leaking capillaries grow under the macula. Although rare, this transition holds significant risk as it causes more rapid and severe vision loss. Oxidative stress is damaging to cellular components and plays a pivotal role in chronic diseases. We aim to determine whether oxidative stress in retinal pigment epithelial (RPE) cells elicits a proangiogenic microenvironment. We exposed human primary RPE cells to hydrogen peroxide (H₂O₂), and we analyzed their metabolic activity, and the production of reactive oxygen species (ROS) and angiogenic factors. In addition, we evaluated the potential of RPE cell-conditioned medium (CM) to induce HUVEC cell tube formation. RPE cells exposed to H₂O₂ displayed a dose-dependent decrease in their metabolic activity, and increased ROS levels. The analysis of the CM of exposed RPE cells revealed differential expression of a panel of proangiogenic factors. Notably, the expression of the major angiogenic factors (VEGF, FGF) was increased. Exposure of HUVEC cells to the CM of H₂O₂-exposed RPE cells promoted tube formation suggestive of microvessel formation. Our findings bring new insights into the role of oxidative stress in altering RPE cell behavior that might have consequences in the progression of AMD towards the exudative form.