title: Long-term Fluorometholone Topical Use Induces Ganglion Cell Damage in Rats Analyzed With Optical Coherence Tomography.
abstract: To determine the toxic effects of long-term topical usage of fluorometholone (FLM) on ganglion cells using a direct in vivo retinopathological Brown Norway (BN) rat model. The BN rat retinal model was investigated with a minimum of 3 rats and a maximum of 4 rats per group. Rats received vehicle and 0.02% FLM suspension via topical administration 3 times a day for 28 days. The fundus images and retinal vessels were detected on days 1, 14, and 28 using Micron III retinal imaging microscope and fundus fluorescein angiography (FFA). For retinal structures, spectral-domain optical coherence tomography (SD-OCT) images were taken after FFA on days 1, 14, and 28 using an SD-OCT Imaging System. For retinal function, electrical signal transduction of photoreceptors and bipolar cells was determined by electroretinographic (ERG) recording on days 1 and 28 and IOP detection. At the end of the experiment on day 28, immunohistochemistry and TUNEL assay were performed to investigate apoptosis in ganglion cells. Total retina and nerve fiber layer (NFL) to the inner plexiform layer (IPL) were significantly thinner following 28 days of FLM treatment. Hematoxylin and eosin stain showed that there were NFL and ganglion cell layer deformations in the FLM group. With FLM treatment, TUNEL assay showed approximately a 4.68-fold increase in apoptotic cells. Moreover, FLM decreased ERG b-wave amplitude by about 56%. Using ophthalmofundoscopy devices, after 28 days of topical administration, FLM decreased NFL-IPL and total retina thickness. This suggests that long-term FLM induces adverse effects with respect to ganglion cell apoptosis.
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan;
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Lin
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
authors.forename: Ching-Hao
authors.initials: CH
authors.lastname: Li
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan;
authors.forename: Shih-Hsuan
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;
authors.forename: Chi-Hao
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan;
authors.forename: Man-Ru
authors.initials: MR
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
authors.forename: Fan-Li
authors.initials: FL
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan; and Department of Ophthalmology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jau-Der
authors.initials: JD
authors.lastname: Ho
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan;
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Cheng
authors.affiliation: *School of Pharmacy, College of Pharmacy, Taipei Medicine University, Taipei, Taiwan; ywcheng@tmu.edu.tw.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004596:Electroretinography; D005469:Fluorometholone / Q000008:administration & dosage / Q000009:adverse effects*; D005654:Fundus Oculi; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D009883:Ophthalmic Solutions; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D005469:Fluorometholone
keywords: chronic; neurotoxicology, toxicity; safety evaluation, ocular toxicity; systems toxicology