Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Efficacy of a new hydroxypropyl-gamma-cyclodextrin-based eyedrop of spironolactone in a rat model of corneal wound healing
Author Affiliations & Notes
  • Daniela Rodrigues-Braz
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
    Valdepharm, Fareva, Val-de-Reuil, France
  • Linxin Zhu
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
  • Emmanuelle Gélizé
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
  • Jean-Pierre Clarin
    Excelvision, Fareva, Annonay, France
  • Xavier Chatagnon
    Excelvision, Fareva, Annonay, France
  • Youcef Benzine
    Valdepharm, Fareva, Val-de-Reuil, France
  • Philippe Rampignon
    Valdepharm, Fareva, Val-de-Reuil, France
  • Jean-Louis Bourges
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
    Ophtalmopole, AP-HP, Cochin Hospital, Paris, France
  • Francine F Behar-Cohen
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
    Ophtalmopole, AP-HP, Cochin Hospital, Paris, France
  • Min Zhao
    Inserm UMRS1138, Team 17, Centre de Recherche des Cordeliers, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Daniela Rodrigues-Braz None; Linxin Zhu None; Emmanuelle Gélizé None; Jean-Pierre Clarin None; Xavier Chatagnon None; Youcef Benzine None; Philippe Rampignon None; Jean-Louis Bourges None; Francine Behar-Cohen None; Min Zhao None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 40. doi:
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      Daniela Rodrigues-Braz, Linxin Zhu, Emmanuelle Gélizé, Jean-Pierre Clarin, Xavier Chatagnon, Youcef Benzine, Philippe Rampignon, Jean-Louis Bourges, Francine F Behar-Cohen, Min Zhao; Efficacy of a new hydroxypropyl-gamma-cyclodextrin-based eyedrop of spironolactone in a rat model of corneal wound healing. Invest. Ophthalmol. Vis. Sci. 2024;65(7):40.

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

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Abstract

Purpose : Abnormal wound healing is a major concern in ophthalmology that can lead to chronic infection and corneal ulceration resulting in corneal opacity and visual impairment. We previously showed that mineralocorticoid receptor (MR) antagonist spironolactone (SPL) is a promising candidate to prevent glucocorticoid-induced delay in corneal wound healing in rabbit. The aim of this study was to evaluate the efficacy of a new polymer free hydroxypropyl-gamma-cyclodextrin-based medical grade eyedrop of SPL in a rat model of corneal wound healing.

Methods : Adult male Sprague-Dawley rats were used. Corneal epithelium was removed in the center 4 mm-diameter of the cornea in both eyes. Rats were divided into 5 groups of treatment: 1) eyedrop containing 0.1% SPL, 2) placebo (PBO) eyedrop, 3) topical potassium canrenoate solution (KCAN, 0.1%), 4) coadministration of dexamethasone (DEX, Dexafree® 0.1%) and SPL eyedrop, and 5) coadministration of DEX and PBO. All treatments were administered 3 times a day for 3 days. Corneal morphology was assessed in vivo using Micron III optical coherence tomography (OCT) immediately (0h), 24 and 48hrs after corneal de-epithelialization. Corneal re-epithelialization was observed at different time points until day 3 by fluorescein staining. At day 5, eyes were collected for immunostaining of inflammation (IBA1, ED1), corneal epithelial integrity (K12, E-cadherin) and corneal nerves (TUBB3).

Results : SPL eyedrop significantly reduced corneal thickness at 48hrs after corneal de-epithelialization and improved corneal re-epithelialization as compared to the PBO and KCAN treatments at 24 and 54 hrs. K12 and E-cadherin immunostaining showed that SPL eyedrop restored corneal epithelial stratification and enhanced epithelial cell adhesion as compared to the PBO. SPL eyedrop significantly reduced the infiltration of IBA1 and ED1-positive inflammatory cells into the cornea and improved the corneal re-innervation as compared to the PBO. SPL eyedrop accelerated corneal wound-healing delayed by DEX.

Conclusions : The new SPL eyedrop is efficient in improving corneal wound healing, reducing inflammation, and restoring epithelial integrity. It could be a promising topical treatment for corneal ulceration of various origins including glucocorticoid-induced wound healing delay.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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