Abstract
Purpose :
Chronic inflammation and oxidative stress are hallmarks in proliferative diabetic retinopathy (PDR) that drive angiogenesis. Nowadays, anti-VEGF therapy is the pharmacological treatment available against aberrant angiogenesis in PDR. In this project, we obtained a nanosuspension (RSV-NS) loaded with resveratrol (RSV), a polyphenol with antioxidant activity. We explored the in vitro anti-inflammatory and antiangiogenic effects of RSV-NS on human microvascular retinal endothelial cells (HMRECs) model, as a potential minimally invasive treatment that can complement current therapies for PDR.
Methods :
Particle size and morphology of RSV-NS were evaluated by dynamic light scattering and scanning transmission electron microscopy. Metabolic activity, cytotoxicity, and proliferation were tested on HMRECs treated with RSV-NS. The anti-inflammatory effect of RSV-NS was evaluated on HMRECs stimulated with 10 ng/mL of tumor necrosis factor-alpha (TNF-a) for one hour through RT-qPCR. Finally, to estimate the antiangiogenic effect, we studied the proliferation, migration, and tube formation under the stimulation of vascular endothelial growth factor (VEGF) at 10 ng/mL.
Results :
RSV-NS had a spherical-like morphology with a uniform monomodal particle size distribution of less than 500 nm on average (Fig. 1A, B). RSV-NS at 18.75 µM significantly reduced the metabolic activity (25.66%, p < 0.0001) and proliferation (51.97%, p < 0.0001) of HMRECs in a dose-dependent manner, without being cytotoxic. Moreover, there was a decrease in the expression of proinflammatory markers when the cells were treated with RSV-NS, compared to the TNF-a-stimulated control (Fig. 1C). Likewise, RSV-NS reduced proliferation, cell migration, and tube formation in the in vitro model stimulated with VEGF (Fig. 1D, E).
Conclusions :
The beneficial properties of RSV were preserved in the formulation, decreasing cell cytotoxicity. RSV-NS exhibited anti-inflammatory and antiangiogenic effects on in vitro models of stress in HMRECs, suggesting the potential of the formulation in future treatments to control pathological ocular angiogenic diseases.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.