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  • The nitric oxide donating triamcinolone acetonide NCX 434 does not increase intraocular pressure and reduces endothelin-1 induced biochemical and functional changes in the rabbit eye

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Laboratory science
Original article
The nitric oxide donating triamcinolone acetonide NCX 434 does not increase intraocular pressure and reduces endothelin-1 induced biochemical and functional changes in the rabbit eye
  1. Francesco Impagnatiello1,
  2. Barbara Giambene2,
  3. Cecilia Lanzi3,
  4. Alessandro Pini4,
  5. Teresa Somma3,
  6. Elena Bastia1,
  7. Ennio Ongini1,
  8. Fernando Galassi2,
  9. Emanuela Masini3
  1. 1NicOx Research Institute, Bresso, Milan, Italy
  2. 2Eye Clinic University of Florence, Florence, Italy
  3. 3Departments of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy
  4. 4Departments of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Florence, Italy
  1. Correspondence to Dr F Impagnatiello, Nicox Research Institute, Via Ariosto 21, Bresso 20091, Milan, Italy, impagnatiello{at}nicox.it; fimpagnatiello{at}hotmail.com

Abstract

Background NCX 434 is a nitric oxide (NO)-donating triamcinolone acetonide (TA), shown to enhance optic nerve head (ONH) oxygen saturation in non-human primate eyes. Here, the effects of a single intravitreal (IVT) injection of TA were compared with those of NCX 434 on intraocular pressure (IOP), retinal function and retrobulbar haemodymamics in endothelin-1 (ET-1) induced ONH ischaemia/reperfusion in rabbits. Biochemical changes were also assessed in the aqueous humour and in retinal biopsies.

Methods IOP and resistivity index of ophthalmic artery (RI-OA) were recorded using TonoPen and ecocolor Doppler, respectively. Retinal function was assessed using photopic electroretinography. Cytokine expression and oxidative stress markers were evaluated with immunoassay techniques.

Results At 4 weeks post IVT treatment, TA increased IOP and RI-OA while NCX 434 did not (IOPVehicle=13.6±1.3, IOPNCX 434=16.9±2.2, IOPTA=20.9±1.9 mm Hg; p<0.05 vs vehicle; RI-OAVehicle=0.44±0.03; RI-OANCX 434=0.47±0.02; RI-OATA=0.60±0.04). Both NCX 434 and TA reversed ET-1 induced decrease in electroretinography amplitude to similar extents. NCX 434 attenuated ET-1 induced oxidative stress markers and nitrotyrosine in retinal tissue, and interleukin-6 and tumour necrosis factor-α in aqueous humour more effectively than TA.

Conclusion NCX 434 attenuates ET-1 induced ischaemia/reperfusion damage without increasing IOP, probably due to NO release. If data are confirmed in other species and models, this compound could represent an interesting new therapeutic option for retinal and ONH diseases, including diabetic retinopathy.

https://doi.org/10.1136/bjophthalmol-2011-300404

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    Footnotes

    • Competing interests EB, FI and EO were employed at Nicox Research Institute at the time this work was performed.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data included in the manuscript are available on request from the corresponding author: impagnatiello{at}nicox.it.