Eye Research Institute, Oakland University, Rochester, MI, 48309, USA.
Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, 37242, USA.
Exp Eye Res. 2021 Sep;210:108697. doi: 10.1016/j.exer.2021.108697. Epub 2021 Jul 4.
Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related αA-crystallin truncation in the lens nucleus. The truncation sites in αA-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract.
高压氧（HBO）治疗动物或培养中的眼晶状体可重现人类年龄相关性核白内障中观察到的许多分子变化。豚鼠 HBO 模型一直是此类治疗导致晶状体核混浊与剂量呈依赖性发展的最佳范例之一。在这项研究中，采用互补的质谱方法来研究 HBO 处理老年豚鼠后的蛋白质截断。豚鼠晶状体膜部分的定量液相色谱-质谱（LC-MS）分析显示，水通道蛋白-0（AQP0）C 端截断显著增加，这与先前报道的膜和细胞骨架蛋白加速丢失一致。此外，成像质谱（IMS）分析在晶状体核中空间定位了年龄相关性αA-晶体蛋白截断的加速。αA-晶体蛋白中的截断位点与年龄相关性人眼晶状体中的观察结果非常吻合。总之，我们的结果表明，HBO 加速了正常晶状体老化过程并导致核白内障。
