Abstract
Purpose: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial–mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients. Methods: Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts. Results: Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients’ lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation. Conclusions: Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM.
Highlights
The International Diabetes Federation estimates that diabetes mellitus (DM) population will reach439 million people in 2030
Refraction and axial length were assessed in 15 patients in the DM group and 15 patients in the non-DM group, while the axial length was measured in 18 DM (+) and 12 DM (−) patients
15 males and 15 females were included in the DM (+) group, while 18 males and 12 females were included in the DM (−) group
Summary
The International Diabetes Federation estimates that diabetes mellitus (DM) population will reach. An aging population and extended patient life expectancy might cause DM patients to exceed 33% by 2050 [1]. Hyperglycemia is a risk factor for numerous diabetic complications, including diabetic cataracts (DCs) development. DCs are characterized by lens opacity and are one of the earliest secondary complications of DM [2,3]. Chronic hyperglycemia leads to osmotic damage, oxidative stress, and non-enzymatic glycation processes in the optical, which are primary drivers for DCs development [2].
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