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Int. J. Mol. Sci. 2017, 18(9), 1971; doi:10.3390/ijms18091971

Therapeutic Effect of Cilostazol Ophthalmic Nanodispersions on Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats

1
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan
2
Laboratory of Molecular Biology and Histochemistry Joint Research Support Promotion Facility Center for Research Promotion and Support Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan
*
Author to whom correspondence should be addressed.
Received: 2 August 2017 / Revised: 4 September 2017 / Accepted: 12 September 2017 / Published: 14 September 2017
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine)
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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. View Full-Text
Keywords: nanoparticle; cilostazol; diabetic retinopathy; electroretinogram; streptozotocin-induced diabetic rat nanoparticle; cilostazol; diabetic retinopathy; electroretinogram; streptozotocin-induced diabetic rat
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Nagai, N.; Deguchi, S.; Otake, H.; Hiramatsu, N.; Yamamoto, N. Therapeutic Effect of Cilostazol Ophthalmic Nanodispersions on Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats. Int. J. Mol. Sci. 2017, 18, 1971.

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