Abstract
We previously prepared ophthalmic formulations containing cilostazol (CLZ) nanoparticles by bead mill methods (CLZnano), and found that instillation of CLZnano into rat eyes supplies CLZ into the retina. In this study, we investigated changes in the electroretinograms (ERG) of streptozotocin-induced diabetic rats (STZ rats), a model of diabetes mellitus. In addition, we demonstrated that dispersions containing CLZ nanoparticles attenuate changes in the ERG of STZ rats. The instillation of CLZnano had no effect on body weight or plasma glucose and insulin levels. Furthermore, no corneal toxicity was observed in the in vivo study using STZ rats. The a-wave and b-wave levels in addition to oscillatory potentials (OP) amplitude decreased in STZ rats two weeks after the injection of streptozotocin, with the instillation of CLZnano attenuating these decreases. In addition, the level of vascular endothelial growth factor (VEGF) in the retinas of STZ rats was 9.26-fold higher than in in normal rats, with this increase also prevented by the instillation of CLZnano Thus, we have found that a-wave and b-wave levels in addition to OP amplitude are decreased in rats following the injection of excessive streptozotocin. Furthermore, the retinal disorders associated with diabetes mellitus are attenuated by the instillation of CLZnano. These findings provide significant information that can be used to design further studies aimed at developing anti-diabetic retinopathy drugs.
Highlights
Diabetes mellitus is a chronic disease that affects a large proportion of people worldwide
Rats was 9.26-fold higher than in in normal rats, with this increase prevented by the instillation of CLZ nanoparticles (CLZnano) we have found that a-wave and b-wave levels in addition to oscillatory potentials (OP) amplitude are decreased in rats following the injection of excessive streptozotocin
These findings provide significant information that can be used to design further studies aimed at developing anti-diabetic retinopathy drugs
Summary
Diabetes mellitus is a chronic disease that affects a large proportion of people worldwide. DR is characterized by a progressive alteration in retinal microvasculature [1], which leads to capillary closure and areas of non-perfusion. Previous studies indicate that the changes in electroretinograms (ERG) were observed in the patients with diabetes, even when they have no symptoms of retinopathy [4,5,6]. Recent studies have found that microstructural changes in the intracranial optic nerve can be observed in the eye of early experimental diabetes before substantial morphological alterations [7,8,9]. The development of therapies for retinal dysfunction caused by diabetes mellitus is expected
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