Murugan Subashree, Cheng Catherine
Indiana University, School of Optometry and Vision Science Program, Bloomington, IN, United States.
Front Cell Dev Biol. 2022 Feb 28;10:852236. doi: 10.3389/fcell.2022.852236. eCollection 2022.
The eye lens is responsible for fine focusing of light onto the retina, and its function relies on tissue transparency and biomechanical properties. Recent studies have demonstrated the importance of Eph-ephrin signaling for the maintenance of life-long lens homeostasis. The binding of Eph receptor tyrosine kinases to ephrin ligands leads to a bidirectional signaling pathway that controls many cellular processes. In particular, dysfunction of the receptor EphA2 or the ligand ephrin-A5 lead to a variety of congenital and age-related cataracts, defined as any opacity in the lens, in human patients. In addition, a wealth of animal studies reveal the unique and overlapping functions of EphA2 and ephrin-A5 in lens cell shape, cell organization and patterning, and overall tissue optical and biomechanical properties. Significant differences in lens phenotypes of mouse models with disrupted EphA2 or ephrin-A5 signaling indicate that genetic modifiers likely affect cataract phenotypes and progression, suggesting a possible reason for the variability of human cataracts due to Eph-ephrin dysfunction. This review summarizes the roles of EphA2 and ephrin-A5 in the lens and suggests future avenues of study.
眼球晶状体负责将光线精确聚焦到视网膜上，其功能依赖于组织的透明度和生物力学特性。最近的研究表明，Eph-ephrin信号传导对于维持晶状体终身稳态至关重要。Eph受体酪氨酸激酶与ephrin配体的结合会导致双向信号通路，该通路控制着许多细胞过程。特别是，受体EphA2或配体ephrin-A5功能失调会导致人类患者出现多种先天性和年龄相关性白内障，白内障定义为晶状体中的任何混浊。此外，大量动物研究揭示了EphA2和ephrin-A5在晶状体细胞形状、细胞组织和模式形成以及整体组织光学和生物力学特性方面的独特和重叠功能。EphA2或ephrin-A5信号传导中断的小鼠模型在晶状体表型上存在显著差异，这表明基因修饰因子可能影响白内障表型和进展，这提示了Eph-ephrin功能障碍导致人类白内障变异性的一个可能原因。本综述总结了EphA2和ephrin-A5在晶状体中的作用，并提出了未来的研究方向。
