Zeaxanthin improves myopia by regulating the HIF-1α-glycolysis signaling pathway

Myopia, a highly prevalent refractive error worldwide, occurs when parallel light rays are refracted by the optical system of the eye and converge in front of the retina, leading to blurred vision, with limited effective intervention options available currently. As a natural small-molecule carotenoid, zeaxanthin (Zea) demonstrates antioxidant and anti-inflammatory properties; however, its involvement in myopia is not yet well understood. Accordingly, this research was designed to examine the effects of Zea in treating myopia and the underlying mechanisms involved. In our research, a myopia cell model was created via treating human scleral fibroblasts (HSFs) with hypoxia (1 % O₂), and a myopia animal model was constructed by using form deprivation methods in Wistar rats. In addition, Zea was administered as a therapeutic intervention. Following the intervention, the cell model was evaluated as follows: HSF viability was assessed using the MTT assay; glucose consumption, lactate production, and extracellular acidification rate were measured using commercial assay kits; and the expression levels of myofibroblast markers, hypoxia-inducible factor 1-alpha (HIF-1α), and key proteins involved in glycolysis were analyzed via Western blot. In the in vivo experiments, ophthalmic instruments were used to evaluate anatomical parameters of the rat eye; scleral thickness was measured using hematoxylin-eosin staining; hypoxia levels in the sclera were assessed using immunofluorescence; and myofibroblast markers, HIF-1α, and key proteins involved in glycolysis were assessed via Western blot. The in vitro assays demonstrated that Zea significantly enhanced the viability of HSFs under hypoxic conditions and inhibited their transformation into myofibroblasts. In the in vivo experiments, Zea effectively improved axial length, refractive error, and vitreous chamber depth in rats, while reversing scleral remodeling and hypoxia. Additionally, both in vivo and in vitro experiments showed that Zea notably diminished the vital protein expression levels in the HIF-1α-glycolysis signaling pathway. Zea improves myopia through modulation of the HIF-1α-glycolysis signaling pathway.