April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Evaluation Of Toxicity Of Anti-glaucoma Drugs Using Stratified Human Cultivated Corneal Epithelial Sheets
Author Affiliations & Notes
  • Suguru Nakagawa
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
    Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Japan
  • Tomohiko Usui
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
  • Seiichi Yokoo
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
  • Sachiko Omichi
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
    JR Tokyo General Hospital, Shibuya-ku, Japan
  • Yosai Mori
    The Department of Ophthalmology, Miyata Eye Hospital, Miyakonojo, Japan
  • Kazunori Miyata
    The Department of Ophthalmology, Miyata Eye Hospital, Miyakonojo, Japan
  • Makoto Aihara
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
  • Shiro Amano
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
  • Makoto Araie
    Ophthalmology, Univ of Tokyo School of Medicine, Bunkyo-ku, Japan
    Kanto Central Hospital, Setagaya-ku, Japan
  • Footnotes
    Commercial Relationships  Suguru Nakagawa, None; Tomohiko Usui, None; Seiichi Yokoo, None; Sachiko Omichi, None; Yosai Mori, None; Kazunori Miyata, None; Makoto Aihara, None; Shiro Amano, None; Makoto Araie, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3110. doi:
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      Suguru Nakagawa, Tomohiko Usui, Seiichi Yokoo, Sachiko Omichi, Yosai Mori, Kazunori Miyata, Makoto Aihara, Shiro Amano, Makoto Araie; Evaluation Of Toxicity Of Anti-glaucoma Drugs Using Stratified Human Cultivated Corneal Epithelial Sheets. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3110.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Because glaucoma patients received anti-glaucoma drugs for many years, the assessment of safe profiles of anti-glaucoma drug is important. We investigated the toxicity profiles of seven antiglaucoma drugs and benzalkonium chloride (BAK) using the stratified human cultivated corneal epithelial sheets in serum-free culture system.

Methods: : The stratified human cultivated corneal epithelial sheets in serum-free culture system were exposed to seven antiglaucoma drugs in their commercial presentation (Latanoprost® (Nitten), LatanoprostPF® (Nitten), TravatanZ® (Alcon), Tapros® (Santen), Xalatan® (Pfizer), DuoTrav® (Alcon), Xalacom® (Pfizer)) and two concentrations (0.002% and 0.02%) of benzalkonium chloride (BAK). Each solution was applied on the cell sheets for 10 minutes. The cell proliferative capacity and barrier function were examined by WST-1 and carboxyfluorescein permeability assays. Histologic evaluation of cell sheets were performed by hematoxylin and eosin (HE) stains after 1 hour, 6 hours, 24 hours application of each solution on the cell sheet.

Results: : Xalatan®, Xalacom® and 0.02%BAK resulted in significantly lower cell proliferation capacity and barrier function than control (P<0.05), but the others did not show significant difference. Cell sheets with 1 hour, 6 hours and 24 hours applications of Xalatan®, Xalacom® and 0.02%BAK were more damaged histologically than the others.

Conclusions: : Xalatan®, Xalacom® and 0.02%BAK have high toxicity in vitro, whereas Latanoprost®, LatanoprostPF®, TravatanZ®, Tapros®, DuoTrav® and 0.002%BAK has very low or no toxicity. This confirms that higher concentrations of BAK were responsible for toxicity. Our assays using the stratified human cultivated corneal epithelial sheets in serum-free culture system are promising methods in ophthalmic toxicology.

Keywords: cornea: epithelium • drug toxicity/drug effects • ocular irritancy/toxicity testing 
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