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.