Abstract
Purpose :
Cataract is a major cause of visual impairment for diabetic patients. It is imperative to develop efficient therapeutic agents against diabetic cataract (DC) because diabetes confers higher risk for complications after cataract surgery. We have previously reported the role of CeCl3 loaded mesoporous silica (CeCl3@mSiO2) nanoparticles in reducing the oxidative stress of lens epithelial cells. However, the potential of CeCl3@mSiO2 in preventing diabetic cataract development remains unclear.This study aimed to evaluate the potential of silica-CeCl3 nanoparticles in the treatment of diabetic cataract in an animal model in vivo.
Methods :
Male Wistar rats were injected intraperitoneally with citrate buffer to serve as controls or streptozotocin (STZ) to develop diabetic cataract lesions. Those animals with blood glucose levels ≥14 mmol/l 7 days after STZ induction were regarded diabetic and treated intraperitoneally with physiological saline (n=20), aminoguanidine at10 mg/kg (n=20), and silica-CeCl3 nanoparticles at 10 mg/kg (n=20) or 20 mg/kg (n=20), respectively, for 10 weeks, during which hyperglycemia-associated cataract progression was assessed by slit lamp biomicroscopy. At the end of the 10-week treatment, animals were sacrificed and oxidative stress and alterations in crystallin protein content in the lens were assessed, and blood levels of glucose and insulin were determined.
Results :
Silica-CeCl3 nanoparticels delayed cataract progression and maturation more effectively than aminoguanidine but failed to prevent STZ-induced hyperglycemia. Silica-CeCl3 nanoparticels also effectively reversed STZ-induced changes in lipid peroxidation as well as protein contents and activities of major antioxidant enzymes. Moreover, silica-CeCl3 nanoparticles effectively prevented aggregation and insolubilization of lens proteins due to formation of advanced glycated end product (AGE). Animals well tolerated the 10-week administration of silic-CeCl3.
Conclusions :
. Our results showed that CeCl3@mSiO2 efficiently ameliorated the progression of DC. Consistent with antioxidant effect of CeCl3@mSiO2in vitro, administration of CeCl3@mSiO2 significantly abrogated hyperglycemia-mediated upregulation of advanced glycation end products, lipid peroxidation and protein carbonylation in animal lens. Taken together, our study provides a potential nanodrug to manage the development of DC.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.