以前的研究表明,硫辛酸等药物具有软化晶状体的能力,为治疗老花眼提供了一条有希望的途径。在此类药物的临床前阶段遇到的一个障碍是需要在实验模型中精确测量晶状体弹性。这项研究旨在评估25-羟基胆固醇的影响,硫辛酸,和奥贝胆酸对使用定制的弹性计系统的小鼠镜片的粘弹性特性。在来自两个年龄组的C57BL/6J雌性小鼠的透镜上获得数据:年轻(年龄:8-10周)和年龄(年龄:32-43周)。OD透镜用作对照,并且处理OS透镜。将对照镜片浸入Dulbecco的改良鹰培养基(DMEM)中,并将治疗镜片浸入含有25-羟基胆固醇(5岁和5岁)的复合溶液中,硫辛酸2.35mM(5岁和5岁),硫辛酸在0.66mM(5岁),或奥贝胆酸(5岁)在37ºC持续18小时。治疗后,将小鼠透镜放置在定制的弹性计系统内的DMEM填充室中,该系统记录当透镜以50μm/s的速度压缩600μm时的载荷和透镜形状。在压缩期间和应力松弛期间连续记录载荷。压缩阶段用线性函数拟合以量化镜片刚度。应力松弛阶段与提供松弛时间常数(t1,t2,t3)的3项指数松弛模型拟合,和平衡负荷。镜头刚度,比较了对照组和治疗组的时间常数和平衡负荷.结果显示,对照组的刚度随年龄增加而增加(年轻:1.16±0.11g/mm,年龄:1.29±0.14g/mm),弛豫时间常数随年龄而降低(年轻:t1=221.9±29.0s,t2=24.7±3.8s,t3=3.12±0.87s,旧:t1=183.0±22.0s,t2=20.6±2.6s和t3=2.24±0.43s)。在测试的化合物中,只有25-羟基胆固醇在晶状体硬度方面产生统计学上显著的变化,弛豫时间常数,和平衡负荷。总之,较旧的鼠标镜片比年轻的鼠标镜片更硬,粘性更低。值得注意的是,用硫辛酸治疗后,未观察到晶状体硬度的显着变化,与以前的发现相反。
Previous studies have shown that pharmaceutical agents such as lipoic acid have the ability to soften the lens, presenting a promising avenue for treating presbyopia. One obstacle encountered in the preclinical stage of such agents is the need for precise measurements of lens elasticity in experimental models. This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system. Data were acquired on lenses from C57BL/6J female mice from two age groups: young (age: 8-10 weeks) and old (age: 32-43 weeks). OD lenses were used as the control and OS lenses were treated. Control lenses were immersed in Dulbecco\'s Modified Eagle Medium (DMEM) and treatment lenses were immersed in a compound solution containing 25-hydroxycholesterol (5 young and 5 old), lipoic acid at 2.35 mM (5 young and 5 old), lipoic acid at 0.66 mM (5 old), or obeticholic acid (5 old) at 37 °C for 18 h. After treatment, the mouse lenses were placed in a DMEM-filled chamber within a custom-built elastometer system that recorded the load and lens shape as the lens was compressed by 600 μm at a speed of 50 μm/s. The load was continuously recorded during
compression and during stress-relaxation. The
compression phase was fit with a linear function to quantify lens stiffness. The stress-relaxation phase was fit with a 3-term exponential relaxation model providing relaxation time constants (t1, t2, t3), and equilibrium load. The lens stiffness, time constants and equilibrium load were compared for the control and treated groups. Results revealed an increase in stiffness with age for the control group (young: 1.16 ± 0.11 g/mm, old: 1.29 ± 0.14 g/mm) and relaxation time constants decreased with age (young: t1 = 221.9 ± 29.0 s, t2 = 24.7 ± 3.8 s, t3 = 3.12 ± 0.87 s, old: t1 = 183.0 ± 22.0 s, t2 = 20.6 ± 2.6 s and t3 = 2.24 ± 0.43 s). Among the compounds tested, only 25-hydroxycholesterol produced statistically significant changes in the lens stiffness, relaxation time constants, and equilibrium load. In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings.