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Toxicity profiles of fixed-combination eye drops for glaucoma therapy using cultivated human corneal epithelial sheets

  • Laboratory Investigation
  • Published:
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Abstract

Purpose

We aimed to investigate the toxicity of 6 fixed-combination drugs for glaucoma therapy using human corneal epithelial sheets (HCES).

Study design

Experimental.

Materials and methods

We used 6 kinds of commercially available fixed-combination drugs: latanoprost/carteolol (LAT/CAR), latanoprost/timolol (LAT/TIM), tafluprost/timolol (TAF/TIM), travoprost/timolol (TRA/TIM), brinzolamide/timolol (BRZ/TIM), and dorzolamide/timolol (DRZ/TIM) including different preservatives. The cell viability and barrier function of the HCES after exposure to the eye drops for 10 or 30 minutes were assessed using the WST-1 assay and transepithelial electrical resistance (TEER) measurements, respectively. The HCES were also evaluated using hematoxylin and eosin (HE) staining and transmission electron microscopy.

Results

The cell viability significantly decreased in the HCES treated with LAT/TIM or DRZ/TIM after 10 and 30 minutes and in those treated with BRZ/TIM after 30 minutes. The barrier function increased significantly in the HCES treated with LAT/CAR. Histologically, the HCES were damaged after treatment with LAT/TIM, BRZ/TIM, or DRZ/TIM for 30 minutes. Transmission electron microscopy indicated narrow intercellular spaces and multiple intercellular junctions in the HCES treated with LAT/CAR, TAF/TIM, or TRA/TIM. The HCES treated with DRZ/TIM, BRZ/TIM, or LAT/TIM contained cytoplasmic vacuoles and collapsed cellular structures.

Conclusion

Glaucoma fixed-combination eye drops demonstrated a different toxic effect on the cell viability, barrier function, and morphologic changes of HCES.

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Acknowledgements

This work was supported by Otsuka Pharmaceutical, Tokyo, Japan.

Conflicts of interest

Y. Hashimoto, None; K. Kitamoto, None; M. Aihara, Grant (Pfizer, Alcon), Lecture fee (Pfizer, Alcon, Santen, HOYA, Abbot, Otsuka, Nitten, Allergan, Crewt Medical Systems, Kowa, Wakamoto, Senju, JFC Sales Plan), Consultant fee (Santen, HOYA, Otsuka, Crewt Medical Systems, Wakamoto, Senju, Glaukos); T. Usui, Grant (Santen, Senju, Alcon, Otsuka).

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Authors and Affiliations

  1. Department of Ophthalmology, University of Tokyo School of Medicine, 1-4-3 Mita, Minato-ku, Tokyo, 108-8329, Japan

    Yumi Hashimoto, Kohdai Kitamoto, Makoto Aihara & Tomohiko Usui

  2. Department of Ophthalmology, International University of Health and Welfare, Tokyo, Japan

    Tomohiko Usui

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  1. Yumi Hashimoto
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  2. Kohdai Kitamoto
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  4. Tomohiko Usui
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Correspondence to Tomohiko Usui.

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Corresponding Author: Tomohiko Usui

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Hashimoto, Y., Kitamoto, K., Aihara, M. et al. Toxicity profiles of fixed-combination eye drops for glaucoma therapy using cultivated human corneal epithelial sheets. Jpn J Ophthalmol 64, 304–311 (2020). https://doi.org/10.1007/s10384-020-00742-3

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  • DOI: https://doi.org/10.1007/s10384-020-00742-3

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