Resveratrol nanoparticles reduce retinal ganglion cell loss in glaucoma

Abstract Purpose Resveratrol is a natural polyphenol found in red wine and dark chocolate known for its antioxidant, anti‐inflammatory and anti‐apoptotic properties. All these properties can be used to treat neurodegenerative diseases such as glaucoma. To date, resveratrol low solubility in water and bioavailability limits its clinical use. The goal of this study was to develop a novel nanoparticle formulation of resveratrol and to assess it in an ocular hypertension (OHT) rat model of glaucoma. Methods Resveratrol nanoparticles (RNs) were formulated using a thin film rehydration technique. OHT rat model was induced with the injection of 1.85 M normal saline solution in two episcleral veins of the left eye of 10 Dark Agouti rats. The right eye was used as an internal control. RNs ( n = 5) or vehicle ( n = 5) were given topically as an eye drop daily for 3 weeks from induction. After 3 weeks, rats were imaged with the Detection of Apoptosing Retinal Cell (DARC) technology. DARC count was defined as the number of apoptosing retinal cells counted by a masked investigator. Next, all rats were sacrificed, and their retinas immunostained with Brn3a antibody. Retinal Ganglion Cell (RGC) density ratio was defined as the ratio between the left treated and the right untreated eye (control). Results RNs were formulated with an encapsulation efficiency >70% and a stability >90 days. They were well‐tolerated without any sign of ocular irritation and neuroprotective in the OHT glaucoma model as evidenced by the reduction of RGC apoptosis compared to the vehicle (1.02 ± 0.05 vs 0.70 ± 0.11 RGC density ratio, p < 0.05). RNs did not reduce the Intraocular Pressure (IOP) suggesting that their effect was independent from IOP modulation. However, RNs were not able to reduce significantly DARC count compared to the vehicle (493 ± 83 vs 612 ± 84 DARC count, p > 0.05). Conclusions These promising results show that topical administration of RNs is neuroprotective in an OHT glaucoma rat model by reducing significantly RGC apoptosis. DARC count reduction is not significant owing to the low number of animals used. Therefore, bigger studies are needed to confirm these encouraging results.