June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Investigating the in vivo effects of topical duloxetine administration in ameliorating corneal neovascularization and neurodegeneration
Author Affiliations & Notes
  • Mojdeh abbasi
    Biomedical and Clinical Sciences, Linkopings universitet Medicinska Fakulteten, Linkoping, Sweden
  • Petros Moustardas
    Biomedical and Clinical Sciences, Linkopings universitet Medicinska Fakulteten, Linkoping, Sweden
  • Dina Javidjam
    Biomedical and Clinical Sciences, Linkopings universitet Medicinska Fakulteten, Linkoping, Sweden
  • Neil Lagali
    Biomedical and Clinical Sciences, Linkopings universitet Medicinska Fakulteten, Linkoping, Sweden
  • Footnotes
    Commercial Relationships   Mojdeh abbasi None; Petros Moustardas None; Dina Javidjam None; Neil Lagali None
  • Footnotes
    Support  AAK-INSIGHT grant from EJP-RD program of the European Union (EJPRD-20-135) and Swedish Research Council (Grant No. 2020-00798)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3127. doi:
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      Mojdeh abbasi, Petros Moustardas, Dina Javidjam, Neil Lagali; Investigating the in vivo effects of topical duloxetine administration in ameliorating corneal neovascularization and neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3127.

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

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Abstract

Purpose : Aniridia is a congenital pan-ocular rare disease with most cases being caused by PAX6 haploinsufficiency. Patients progressively develop keratopathy, characterized by loss of transparency and vessel ingrowth that leads to vision loss. The keratopathy also leads to impaired corneal innervation and inflammation. Recently duloxetine, a serotonin reuptake inhibitor and FDA-approved drug applied for severe depression was shown to enhance the PAX6 protein level in vitro. Accordingly, in this study, we aimed to investigate the effect of duloxetine delivered topically to the murine cornea on inflammation, neurodegeneration, and neovascularization using a suture-induced corneal neovascularization (CorNV) model.

Methods : CorNV was induced using 3 sutures placed in the cornea of wild-type C57Bl/6 male mice followed by topical administration of duloxetine (10 µM) 2 times a day for 10 days. On day 10, the status of inflammation was assessed using in vivo confocal microscopy and whole-mount corneal tissues were double-stained with the neuronal-specific marker, beta III Tubulin, and endothelial-specific marker, CD31.

Results : Pax6 had a higher expression in duloxetine-treated corneas and was expressed in more epithelial layers compared to controls where it was confined to the basal epithelium. There was a considerable increase in neovascular response after CorNV in PBS-treated mice. However, we observed a tendency towards a decline in neovascularization in the corneas treated with duloxetine, though the result was not statistically significant. We also detected a significant reduction in corneal subbasal nerves following suturing, compared to non-sutured corneas (*p<0.05), while duloxetine did not appear to have an ameliorating effect. Although inflammatory cell migration was increased following suturing, no substantial difference in inflammatory cell invasion was noted between groups.

Conclusions : Duloxetine applied topically to the mouse cornea enhances PAX6 protein expression in vivo, however, its application in the wild-type mouse cornea was not sufficient to promote neuronal regeneration, and reduce neovascularization or inflammatory cell infiltration after an acute wound. Further investigation in a chronic wound healing model and haploinsufficient mice is needed prior to the development of duloxetine-based topical therapy for aniridia.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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