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Research ArticleEndocrine and Diabetes

Neuroprotective Effects of Cilostazol on Retinal Ganglion Cell Damage in Diabetic Rats

Kyoung In Jung, Jie Hyun Kim, Hae-Young Lopilly Park and Chan Kee Park
Journal of Pharmacology and Experimental Therapeutics June 2013, 345 (3) 457-463; DOI: https://doi.org/10.1124/jpet.113.203067
Kyoung In Jung
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Jie Hyun Kim
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Hae-Young Lopilly Park
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Chan Kee Park
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Abstract

Neurodegeneration is an important component of diabetic retinopathy, with increasing evidence that retinal ganglion cell (RGC) death occurs early in diabetes. We investigated the effects of cilostazol, which has been widely used to manage diabetic complications, on retinal ganglion cell death in the diabetic retina. Four-week-old Otsuka Long-Evans Tokushima fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats as matched nondiabetic controls were treated with daily oral cilostazol at 30 mg/kg or 0.9% saline solution. In OLETF rats at the age of 40 weeks, glial fibrillary acidic protein (GFAP) immunofluorescence staining was upregulated in vertical sections, and showed a more ramified pattern in whole-mount retinas compared with that in LETO rats. Vascular endothelial growth factor (VEGF) expression was limited to the ganglion cell layer in LETO rats, but extended into the outer plexiform layer in OLETF rats. Immunofluorescence staining and Western blotting demonstrated that cilostazol treatment reduced GFAP and VEGF expression in the retinas of OLETF rats. Terminal deoxynucleotidyl transferase-mediated terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL) staining revealed an increase in the RGC layer in OLETF compared with LETO rats (P < 0.05), and cilostazol treatment reduced the number of TUNEL-positive cells in OLETF rats (P < 0.05). Relieving retinal ischemia by systemic cilostazol treatment had a noticeable protective effect on RGCs in diabetic rats. Cilostazol treatment may be useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration.

Footnotes

    • Received January 7, 2013.
    • Accepted March 26, 2013.
  • K.I.J. and J.H.K. contributed equally to this work.

  • This work was supported by a National Research Foundation of Korea grant funded by the Korean government (Ministry of Education, Science and Technology) [Grant 20120001399]; and Otsuka Pharmaceutical Co. (Tokushima, Japan).

  • dx.doi.org/10.1124/jpet.113.203067.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 345 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 3
1 Jun 2013
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Research ArticleEndocrine and Diabetes

Neuroprotective Effects of Cilostazol in Diabetic Retina

Kyoung In Jung, Jie Hyun Kim, Hae-Young Lopilly Park and Chan Kee Park
Journal of Pharmacology and Experimental Therapeutics June 1, 2013, 345 (3) 457-463; DOI: https://doi.org/10.1124/jpet.113.203067

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Research ArticleEndocrine and Diabetes

Neuroprotective Effects of Cilostazol in Diabetic Retina

Kyoung In Jung, Jie Hyun Kim, Hae-Young Lopilly Park and Chan Kee Park
Journal of Pharmacology and Experimental Therapeutics June 1, 2013, 345 (3) 457-463; DOI: https://doi.org/10.1124/jpet.113.203067
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