Wen Xiaoying, Yang Na, Gu Chaohui, Zhang Yimeng, Hao Yuhua
Department of Ophthalmology, Baoding NO.1 Central Hospital, Baoding, 071000, Hebei, China.
Department of Ophthalmology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050010, Hebei, China.
Exp Eye Res. 2025 Oct;259:110557. doi: 10.1016/j.exer.2025.110557. Epub 2025 Jul 28.
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 % O), 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.
近视是一种在全球范围内高度流行的屈光不正，当平行光线被眼睛的光学系统折射并在视网膜前汇聚时就会发生近视，导致视力模糊，目前有效的干预选择有限。作为一种天然的小分子类胡萝卜素，玉米黄质（Zea）具有抗氧化和抗炎特性；然而，其在近视中的作用尚未得到充分了解。因此，本研究旨在探讨玉米黄质治疗近视的效果及其潜在机制。在我们的研究中，通过用低氧（1% O）处理人巩膜成纤维细胞（HSFs）建立了近视细胞模型，并在Wistar大鼠中使用形觉剥夺方法构建了近视动物模型。此外，给予玉米黄质作为治疗干预。干预后，对细胞模型进行如下评估：使用MTT法评估HSF活力；使用商业检测试剂盒测量葡萄糖消耗、乳酸产生和细胞外酸化率；通过蛋白质印迹分析肌成纤维细胞标志物、缺氧诱导因子1α（HIF-1α）和参与糖酵解的关键蛋白的表达水平。在体内实验中，使用眼科仪器评估大鼠眼睛的解剖参数；使用苏木精-伊红染色测量巩膜厚度；使用免疫荧光评估巩膜中的缺氧水平；通过蛋白质印迹评估肌成纤维细胞标志物、HIF-1α和参与糖酵解的关键蛋白。体外实验表明，玉米黄质在低氧条件下显著提高了HSF的活力，并抑制了它们向肌成纤维细胞的转化。在体内实验中，玉米黄质有效地改善了大鼠的眼轴长度、屈光不正和玻璃体腔深度，同时逆转了巩膜重塑和缺氧。此外，体内和体外实验均表明，玉米黄质显著降低了HIF-1α-糖酵解信号通路中的关键蛋白表达水平。玉米黄质通过调节HIF-1α-糖酵解信号通路改善近视。
