Castro Natalia, Peña Juan S, Cliver Richard, Berthiaume François, Vazquez Maribel
Rutgers, The State University of New Jersey, Department of Biomedical Engineering, USA.
The University of Iowa, Department of Biomedical Engineering, USA.
Exp Eye Res. 2025 Feb;251:110185. doi: 10.1016/j.exer.2024.110185. Epub 2024 Nov 29.
Diabetic retinopathy is a leading cause of vision loss in working adults, with disproportionate impact on women with lowered estrogen. Sex hormones and their receptors are significant to neuroprotection of the inner blood-retinal barrier (iBRB), a tissue that regulates transport across the neuroretina and vasculature. Moreover, high glucose levels in diabetes lead to the formation of advanced glycation end products (AGEs), which promote inflammation and iBRB breakdown to result in vision loss. This study examined the effects of supplemental estradiol on cell reactivity and cell barrier resistance within an in vitro model of hyperglycemia. Changes in morphology and expression of reactive oxygen species were examined when cells were exposed to a hyperglycemic medium containing AGEs, with and without supplemental estradiol. Cell morphology was assessed via changes in cell area and cell shape index, while intracellular ROS levels were measured using a ROS-sensitive dye. In addition, trans endothelial resistance (TEER) assays were used to measure changes in cell barrier function in response to hyperglycemic conditions, with and without supplemental estradiol. Results show that ROS levels in Müller glia in hyperglycemic conditions significantly decreased in response to supplemental estradiol. The estradiol further increased the resistivity of Müller glia and endothelial cell barriers cultured in high glucose and AGEs. This project illustrates the restorative effects of estradiol in collective responses of cell barriers formed by endothelial cells and Müller glia.
糖尿病视网膜病变是在职成年人视力丧失的主要原因，对雌激素水平降低的女性影响尤为严重。性激素及其受体对血视网膜内屏障（iBRB）的神经保护作用至关重要，血视网膜内屏障是一种调节神经视网膜和血管间物质运输的组织。此外，糖尿病患者的高血糖水平会导致晚期糖基化终产物（AGEs）的形成，AGEs会促进炎症反应并破坏血视网膜内屏障，从而导致视力丧失。本研究在高血糖体外模型中研究了补充雌二醇对细胞反应性和细胞屏障抗性的影响。当细胞暴露于含有AGEs的高血糖培养基中时，检测有无补充雌二醇情况下细胞形态和活性氧表达的变化。通过细胞面积和细胞形状指数的变化评估细胞形态，同时使用对活性氧敏感的染料测量细胞内活性氧水平。此外，使用跨内皮电阻（TEER）测定法测量有无补充雌二醇时，细胞屏障功能对高血糖条件的反应变化。结果表明，补充雌二醇后，高血糖条件下 Müller 胶质细胞中的活性氧水平显著降低。雌二醇进一步提高了在高糖和AGEs环境中培养的 Müller 胶质细胞和内皮细胞屏障的电阻。该项目说明了雌二醇对由内皮细胞和 Müller 胶质细胞形成的细胞屏障集体反应的修复作用。
