title: Neuroprotective effects of cilostazol on retinal ganglion cell damage in diabetic rats.
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.
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, Korea.
authors.forename: Kyoung In
authors.initials: KI
authors.lastname: Jung
authors.forename: Jie Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Hae-Young Lopilly
authors.initials: HY
authors.lastname: Park
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D000077407:Cilostazol; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D020334:Rats, Inbred OLETF; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D000077407:Cilostazol