Abstract
Oxidative stress induced by decreases in tear volume and excessive tear evaporation is a key factor in dry eye disease (DED). Previously, we reported that desiccation stress induces reactive oxygen species generation and up-regulated expression of age-related markers such as p53, p21 and p16. We also showed that the antioxidant astaxanthin prepared as a liposomal formulation could suppress these phenomena in the in vitro DED model. In this study, we evaluated the protective effect of liposomes encapsulating astaxanthin against superficial punctate keratopathy (SPK) in the in vivo rat DED model. This model of DED was characterized by decreased tear volume and increased fluorescein score as an indicator of SPK as well as upregulated expression of age-related markers. Repeat-dose of liposomal astaxanthin prevented increases in the fluorescein score and up-regulation of age-related markers. Liposomes bearing a slight positive surface charge had superior effects and higher affinity compared to neutral liposomes. Furthermore, fluorescence intensities in rat corneal epithelium after administration of high-affinity liposomes labeled with fluorescent dye were higher than those for neutral liposomes. In conclusion, we developed the high-affinity liposomal formulation that can prevent DED and promote antioxidative effects of astaxanthin.