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.

Original languageEnglish
Article numberkfv132
Pages (from-to)317-325
Number of pages9
JournalToxicological Sciences
Volume147
Issue number2
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Fluorometholone
Optical tomography
Optical Coherence Tomography
Ganglia
Rats
Cells
Nerve Fibers
Topical Administration
Angiography
Fluorescein Angiography
In Situ Nick-End Labeling
Fluorescein
Retina
Fibers
Assays
Apoptosis
Retinal Vessels
Signal transduction
Photoreceptor Cells
Poisons

Keywords

  • chronic
  • Neurotoxicology
  • ocular toxicity
  • safety evaluation
  • systems toxicology
  • toxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

Long-term Fluorometholone Topical Use Induces Ganglion Cell Damage in Rats Analyzed With Optical Coherence Tomography. / Lin, Cheng Hui; Liao, Po Lin; Hsiao, George; Li, Ching Hao; Huang, Shih Hsuan; Tsai, Chi Hao; Wu, Man Ru; Lin, Fan Li; Ho, Jau Der; Cheng, Hui Wen; Cheng, Yu Wen.

In: Toxicological Sciences, Vol. 147, No. 2, kfv132, 01.10.2015, p. 317-325.

Research output: Contribution to journalArticle

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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.",
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AU - Huang, Shih Hsuan

AU - Tsai, Chi Hao

AU - Wu, Man Ru

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