School of Optometry and Vision Science Program, Indiana University, Bloomington, Indiana, United States.
Invest Ophthalmol Vis Sci. 2021 Dec 1;62(15):3. doi: 10.1167/iovs.62.15.3.
Fine focusing of light by the eye lens onto the retina relies on the ability of the lens to change shape during the process of accommodation. Little is known about the cellular structures that regulate elasticity and resilience. We tested whether Eph-ephrin signaling is involved in lens biomechanical properties.
We used confocal microscopy and tissue mechanical testing to examine mouse lenses with genetic disruption of EphA2 or ephrin-A5.
Confocal imaging revealed misalignment of the suture between each shell of newly added fiber cells in knockout lenses. Despite having disordered sutures, loss of EphA2 or ephrin-A5 did not affect lens stiffness. Surprisingly, knockout lenses were more resilient and recovered almost completely after load removal. Confocal microscopy and quantitative image analysis from live lenses before, during, and after compression revealed that knockout lenses had misaligned Y-sutures, leading to a change in force distribution during compression. Knockout lenses displayed decreased separation of fiber cell tips at the anterior suture at high loads and had more complete recovery after load removal, which leads to improved whole-lens resiliency.
EphA2 and ephrin-A5 are needed for normal patterning of fiber cell tips and the formation of a well-aligned Y-suture with fiber tips stacked on top of previous generations of fiber cells. The misalignment of lens sutures leads to increased resilience after compression. The data suggest that alignment of the Y-suture may constrain the overall elasticity and resilience of the lens.
眼睛晶状体将光线精确定焦在视网膜上依赖于晶状体在调节过程中改变形状的能力。对于调节弹性和弹性恢复的细胞结构知之甚少。我们测试了 Eph-ephrin 信号是否参与晶状体生物力学特性。
我们使用共聚焦显微镜和组织力学测试来检查 EphA2 或 ephrin-A5 基因敲除的小鼠晶状体。
共聚焦成像显示，在敲除的晶状体中，每个新添加的纤维细胞壳之间的缝线不对齐。尽管缝线排列紊乱，但 EphA2 或 ephrin-A5 的缺失并不影响晶状体的硬度。令人惊讶的是，敲除的晶状体更有弹性，在负载移除后几乎完全恢复。在压缩前、压缩中和压缩后对活体晶状体进行共聚焦显微镜和定量图像分析显示，敲除的晶状体的 Y 缝线不对齐，导致在压缩过程中力分布发生变化。在高负荷下，敲除的晶状体的前部缝线处纤维细胞尖端分离减少，在负载移除后恢复更完全，从而提高了整个晶状体的弹性。
EphA2 和 ephrin-A5 对于纤维细胞尖端的正常排列以及形成与纤维尖端堆叠在上一代纤维细胞之上的对齐良好的 Y 缝线是必需的。晶状体缝线的不对齐导致压缩后弹性增加。数据表明，Y 缝线的对齐可能会限制晶状体的整体弹性和弹性恢复。
