An injectable hyaluronic acid hydrogel protects against retinal pigment epithelial injury induced by sodium iodate

Abstract

The oxidative stress-induced degeneration of the retinal pigment epithelium (RPE) and secondary photoreceptor damage are the main causes of dry age-related macular degeneration (AMD). No effective interventions are currently available for use in clinical practice. Therefore, the aim of this study was to design and evaluate the effects of an injectable hyaluronic acid (HA) hydrogel containing the natural antioxidant myricetin (MY) using both in vitro and in vivo models. To improve the solubility of MY, MY-cyclodextrin (CD) complexes were prepared via host-guest interactions. MY-loaded injectable hydrogel (H-MY) sustained-release formulations were fabricated using adipic acid dihydrazide-modified HA and aldehyde-functionalized HA. Intravitreal injection of the HA hydrogel prolonged the retention time of MY in the eyes of mice, without damaging the normal physiological structures and functions of the organ. Compared with the NaIO₃-treated group, the percentage of reactive oxygen species (ROS)-positive cells in the H-MY-treated group decreased from 30.7 % to 3.21 %, indicating effective inhibition of intracellular ROS production. And the JC-1 aggregation ratio in the H-MY-treated group increased from 49.4 % to 71.9 %, reflecting a notable alleviation of mitochondrial damage. Meanwhile, the proportion of apoptotic cells was reduced from 37.1 % to 25.3 %, demonstrating a significant decrease in cell apoptosis rate. Furthermore, a NaIO₃-induced acute oxidative stress model of retinal degeneration in mice was employed. In this model, intravitreal injection of the H-MY significantly protected retinal structure and preserved tissue physiological functionality. The HA hydrogel has been observed to exhibit modest antioxidant activity, along with acceptable biocompatibility and stability under experimental conditions. These characteristics suggest that it may offer certain reference significance for clinical management of dry AMD.