IMR Press / FBL / Volume 27 / Issue 5 / DOI: 10.31083/j.fbl2705147
Open Access Original Research
In Vitro Corneal and Conjunctival Wound-Healing Assays as a Tool for Antiglaucoma Prostaglandin Formulation Characterization
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1 Institut de la Vision, Sorbonne Université, INSERM, CNRS, IHU Foresight, 75012 Paris, France
2 Quinze-Vingts National Ophthalmology Hospital, IHU Foresight, 75012 Paris, France
3 University of Versailles Saint Quentin en Yvelines, 78000 Versailles, France
4 Santen SAS, 91000 Evry, France
5 Toxicology Department, Faculty of Pharmaceutical and Biological Sciences, Paris Descartes University, 75006 Paris, France
*Correspondence: lianghongfr@yahoo.fr (Hong Liang)
Academic Editors: Shikun He and Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(5), 147; https://doi.org/10.31083/j.fbl2705147
Submitted: 26 December 2021 | Revised: 5 February 2022 | Accepted: 16 February 2022 | Published: 7 May 2022
(This article belongs to the Special Issue Recent Advances in Eye and Vision Research)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Benzalkonium chloride (BAK)-containing antiglaucoma therapies alter the ocular surface over the long term. We used an in vitro scraping model to compare the effects of preserved and unpreserved topical commercial prostaglandins (PGs) in a wound-healing model. Methods: Standardized mechanical scraping was performed in confluent immortalized human corneal/conjunctival epithelial cell layers. Cytotoxicity, cell migration and proliferation, as well as the percentage of closure, were analyzed 2h and 1/2/3/6 days after a 30-min exposure to 1/10 dilutions in phosphate buffered saline (PBS) used also as control, BAK solutions at concentrations ranging from 0.0001% to 0.1%, latanoprost-0.02%BAK, travoprost-0.015%BAK, bimatoprost-0.005%BAK, BAK-free Tafluprost, latanoprost in cationic emulsion, and travoprost (Polyquad® and SofZia®). Results: PG eyedrop preparations with BAK preservative delayed corneal healing, which is primarily related to the presence of BAK, in a dose-dependent manner, especially at day 1, as evidenced through actin disorganization and decreased Ki-67-positive cell numbers. The PGs (BAK-free tafluprost, latanoprost in cationic emulsion,travoprost (Polyquad® and SofZia®)) maintained a normal healing process with results similar to those of control. Conjunctiva-derived cell layers healed more slowly than corneal cell layers and were more sensitive in in vitro cytotoxicity tests. Conclusions: This novel in vitro scraping model mimics the damaged ocular surface epithelia observed in glaucoma patients affected by ocular surface disease, such as toxic-induced dry eye (TIDE) and offers a tool to assess the potential cytotoxic effects of PG formulations with or without BAK.

Keywords
cornea
conjunctiva
wound-healing
antiglaucoma prostaglandin
Figures
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