Resveratrol nanoparticles are neuroprotective in a rat model of 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 Cells (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. RN treatment was found to significantly reduce RGC loss 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 neuroprotective effect was independent of IOP, although this effect was not found to be significant in the 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 was neuroprotective and well-tolerated in an OHT glaucoma rat model by reducing significantly RGC loss. This effect appears to be independent of IOP, but was not seen in the DARC count. We suggest larger studies are needed to confirm these encouraging results.

This is a 2021 ARVO Annual Meeting abstract.