June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
NCX 470, a nitric oxide (NO)-donating bimatoprost, preserves rabbit eyes from biochemical and functional changes associated with endothelin-1 (ET-1)-induced ischemia/reperfusion injury of optic nerve head and retina
Author Affiliations & Notes
  • Francesco Impagnatiello
    NicOx Research Institute Srl, Bresso, Lombardia, Italy
  • Corinna Galli
    NicOx Research Institute Srl, Bresso, Lombardia, Italy
  • Silvia Sgambellone
    NEUROFARBA, University of Florence, Florence, Italy
  • Silvia Marri
    NEUROFARBA, University of Florence, Florence, Italy
  • Emanuela Masini
    NEUROFARBA, University of Florence, Florence, Italy
  • Gustavo Provensi
    NEUROFARBA, University of Florence, Florence, Italy
  • Elena Bastia
    NicOx Research Institute Srl, Bresso, Lombardia, Italy
  • Stefania Brambilla
    NicOx Research Institute Srl, Bresso, Lombardia, Italy
  • Doug Hubatsch
    Nicox Ophthalmics, Durham, North Carolina, United States
  • Laura Lucarini
    NEUROFARBA, University of Florence, Florence, Italy
  • Footnotes
    Commercial Relationships   Francesco Impagnatiello Nicox Research Institute, Code E (Employment); Corinna Galli Nicox Research Institute, Code E (Employment); Silvia Sgambellone None; Silvia Marri None; Emanuela Masini None; Gustavo Provensi None; Elena Bastia Nicox Research Institute, Code E (Employment); Stefania Brambilla Nicox Research Institute, Code E (Employment); Doug Hubatsch Nicox Ophthalmics, Code E (Employment); Laura Lucarini None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2580. doi:
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      Francesco Impagnatiello, Corinna Galli, Silvia Sgambellone, Silvia Marri, Emanuela Masini, Gustavo Provensi, Elena Bastia, Stefania Brambilla, Doug Hubatsch, Laura Lucarini; NCX 470, a nitric oxide (NO)-donating bimatoprost, preserves rabbit eyes from biochemical and functional changes associated with endothelin-1 (ET-1)-induced ischemia/reperfusion injury of optic nerve head and retina. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2580.

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

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Abstract

Purpose : NCX 470, a nitric oxide (NO)-donating bimatoprost, ameliorates ocular hemodynamics and retinal physiology after endothelin-1 (ET-1)-induced ischemia/reperfusion injury of retina (RE) and optic nerve head (ONH). Here we confirmed previous findings and compared NCX 470 (0.1% bid, 6 days/week) to Lumigan® (LUM, bimatoprost 0.01%, ophthalmic solution) and bimatoprost administered at the equimolar dose as released by 0.1% NCX 470 (BIM, 0.072%). Moreover, we investigated whether inhibition of inflammatory cytokines and reduction of apoptosis accounts for NCX 470-mediated activity.

Methods : ET-1 was injected near the ONH twice/week/6-weeks while NCX 470, LUM, BIM or vehicle treatments started on week-3 and continued until week-6. Ophthalmic artery resistive index (OA-RI) and scotopic cones/rods responses (ERG) were determined prior to treatment and at various time-points thereafter using an Echo-Color-Doppler and a Retimax apparatus. Interlukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) were determined in dissected RE at week-6 via ELISA. Caspase-3 was determined at week-6 monitoring the conversion of relevant fluorescent substrate.

Results : ET-1 increased OA-RI (0.36±0.02 and 0.55±0.01 at baseline and week-6, respectively). NCX 470 prevented OA-RI increase (0.33±0.01) while LUM and BIM resulted partially effective (0.43±0.02 and 0.44±0.01). Rods/cones responses declined following ET-1 (139.5±17.8 and 89.1±10.7µV at baseline and week-6). NCX 470-treated eyes exhibited less impairment (124.1±11.3µV) compared to eyes dosed with vehicle while neither LUM (112.05±5.6µV) nor BIM (89.3±9.0µV) resulted effective. IL-1β, TNFα and Caspase-3 increased in ET-1-treated eyes; NCX 470 restored baseline levels of these markers, an effect not equally seen in LUM- and BIM-treated eyes.

Conclusions : NCX 470 is a dual-acting drug holding promise for the treatment of ocular hypertension and glaucoma with beneficial effects on ocular hemodynamics and retinal cell function.

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

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