Faculty of Pharmacy, Keio University, 1-5-30 Shibako Minato-ku, Tokyo 105-8512, Japan.
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Cells. 2021 Feb 12;10(2):382. doi: 10.3390/cells10020382.
Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear. With age, water microcirculation in the lens could change because of an increase in intracellular pressure. In the lens, the intracellular pressure is controlled by the Transient Receptor Potential Vanilloid (TRPV) 1 and TRPV4 feedback pathways. In this study, we tried to elucidate that administration of α-glucosyl-hesperidin (G-Hsd), previously reported to prevent nuclear cataract formation, affects lens elasticity and the distribution of TRPV channels and Aquaporin (AQP) channels to meet the requirement of intracellular pressure. As a result, the mouse control lens was significantly toughened compared to both the 1% and 2% G-Hsd mouse lens treatments. The anti-oxidant levels in the lens and plasma decreased with age; however, this decrease could be nullified with either 1% or 2% G-Hsd treatment in a concentration- and exposure time-dependent manner. Moreover, G-Hsd treatment affected the TRPV4 distribution, but not TRPV1, AQP0, and AQP5, in the peripheral area and could maintain intracellular pressure. These findings suggest that G-Hsd has great potential as a compound to prevent presbyopia and/or cataract formation.
老视的特征是晶状体调节能力下降。最常被接受的老视发病理论是晶状体随年龄增长而变硬。然而，晶状体硬化的确切原因仍不清楚。随着年龄的增长，晶状体中水的微循环可能会因细胞内压力增加而发生变化。在晶状体中，细胞内压力由瞬时受体电位香草酸 (TRPV) 1 和 TRPV4 反馈途径控制。在这项研究中，我们试图阐明先前报道可预防核性白内障形成的α-葡萄糖基橙皮苷 (G-Hsd) 的给药如何影响晶状体弹性以及 TRPV 通道和水通道蛋白 (AQP) 通道的分布，以满足细胞内压力的要求。结果表明，与 1%和 2% G-Hsd 处理的小鼠晶状体相比，对照小鼠晶状体明显变硬。随着年龄的增长，晶状体和血浆中的抗氧化水平下降；然而，用 1%或 2% G-Hsd 处理可以在浓度和暴露时间依赖性的方式下消除这种下降。此外，G-Hsd 处理影响外周区域 TRPV4 的分布，但不影响 TRPV1、AQP0 和 AQP5，并且可以维持细胞内压力。这些发现表明 G-Hsd 具有作为预防老视和/或白内障形成的化合物的巨大潜力。
