Increased oxidative stress and inflammation play an important role in the pathogenesis of diabetic cataract. Klotho, known as an anti-ageing protein, has antioxidative and anti-inflammatory properties. Klotho is expressed in limited tissues including the lens. Here we examined whether klotho expression is decreased in diabetic lens and, if so, whether klotho treatment can prevent diabetic cataract formation. Streptozotocin (STZ)-induced diabetic rats and age-matched control rats were treated with vehicle or klotho protein, starting at 1 week after STZ injection. Twelve weeks after treatment, cataract formation was observed in diabetic rats but not control rats. Cataract formation and scores were significantly less in klotho-treated diabetic rats than vehicle-treated diabetic rats. Levels of klotho in plasma, aqueous humor and lens were significantly decreased in vehicle-treated diabetic rats, compared with control rats, but were restored in klotho-treated diabetic rats. Additionally, vehicle-treated diabetic rats had increased oxidative stress and inflammation in the lens, which were associated with decreased antioxidant transcriptional master regulator Nrf2 activity and increased transcription factor NF-κB activity. All of these findings were ameliorated in klotho-treated diabetic rats. Notably, klotho treatment did not alter blood glucose in diabetic rats. These results indicate that klotho reduction may increase susceptibility of the lens to oxidative and inflammatory insults, promoting cataract formation under diabetic conditions. Klotho treatment can ameliorate the onset and progression of diabetic cataract via enhancing Nrf2-mediated antioxidant defense and suppressing NF-κB-mediated inflammatory responses. Klotho in the lens may be a novel therapeutic target for prevention of cataract formation in diabetes.

氧化应激和炎症的增加在糖尿病性白内障的发病机理中起重要作用。Klotho被称为抗衰老蛋白，具有抗氧化和抗炎特性。Klotho在包括晶状体在内的有限组织中表达。在这里，我们检查了糖尿病晶状体中klotho的表达是否降低，如果是的话，klotho的治疗是否可以预防糖尿病性白内障的形成。从STZ注射后1周开始，用媒介物或klotho蛋白治疗链脲佐菌素（STZ）诱导的糖尿病大鼠和年龄匹配的对照大鼠。治疗后十二周，在糖尿病大鼠中观察到白内障形成，但在对照大鼠中未观察到白内障形成。在用klotho治疗的糖尿病大鼠中，白内障形成和评分显着低于用媒介物治疗的糖尿病大鼠。血浆中klotho的水平 与对照大鼠相比，用赋形剂治疗的糖尿病大鼠的房水和晶状体明显减少，但在用克洛他治疗的糖尿病大鼠中房水和晶状体恢复。另外，用赋形剂治疗的糖尿病大鼠具有增加的晶状体氧化应激和炎症，这与抗氧化剂转录主调节因子Nrf2活性降低和转录因子NF-κB活性升高有关。所有这些发现在用克洛索治疗的糖尿病大鼠中得到改善。值得注意的是，klotho治疗并没有改变糖尿病大鼠的血糖。这些结果表明，克洛索减少可能会增加晶状体对氧化性和炎性损伤的敏感性，从而促进糖尿病条件下白内障的形成。Klotho治疗可通过增强Nrf2介导的抗氧化剂防御和抑制NF-κB介导的炎症反应来改善糖尿病性白内障的发作和进展。晶状体中的Klotho可能是预防糖尿病中白内障形成的新型治疗靶标。