Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.

晶状体中的蛋白质的更新可以忽略不计，因此在老化过程中会逐渐积累化学修饰。羰基化合物和氧化应激相互错综复杂地联系在一起，主要推动了这种修饰。氧化应激导致谷胱甘肽 (GSH) 损失和抗坏血酸降解；这反过来导致形成高反应性二羰基化合物，这些化合物与蛋白质反应形成高级糖基化终产物 (AGEs)。AGEs 的形成导致蛋白质的交联和聚集，从而导致晶状体老化和白内障的形成。为了抑制 AGE 的形成，我们开发了一种连接 GSH 二酯和巯基乙基胍的二硫化物，我们将其命名为 carboxitin。用羧化素培养的牛晶状体器官在晶状体核中显示出较高水平的 GSH 和巯基乙基胍。Carboxitin 抑制赤藓酮糖介导的小鼠晶状体蛋白交联、AGE 形成和 3-脱氧苏酮的形成，这是人类晶状体中主要的抗坏血酸衍生 AGE 前体。Carboxitin 抑制了使用压缩机械应变测量的器官培养小鼠晶状体中糖化介导的刚度增加。将羧化素输送到晶状体中会增加 GSH 水平，捕获二羰基化合物并抑制 AGE 形成。carboxitin 的这些特性可用于开发一种治疗方法，以对抗 AGEs 的形成和刚度的增加，从而导致老化镜片中的老花眼。Carboxitin 抑制了使用压缩机械应变测量的器官培养小鼠晶状体中糖化介导的刚度增加。将羧化素输送到晶状体中会增加 GSH 水平，捕获二羰基化合物并抑制 AGE 形成。carboxitin 的这些特性可用于开发一种治疗方法，以对抗 AGEs 的形成和刚度的增加，从而导致老化镜片中的老花眼。Carboxitin 抑制了使用压缩机械应变测量的器官培养小鼠晶状体中糖化介导的刚度增加。将羧化素输送到晶状体中会增加 GSH 水平，捕获二羰基化合物并抑制 AGE 形成。carboxitin 的这些特性可用于开发一种治疗方法，以对抗 AGEs 的形成和刚度的增加，从而导致老化镜片中的老花眼。