Br J Ophthalmol doi:10.1136/bjophthalmol-2011-300404
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
+ Author Affiliations
1NicOx Research Institute, Bresso, Milan, Italy
2Eye Clinic University of Florence, Florence, Italy
3Departments of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy
4Departments of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Florence, Italy
Correspondence to Dr F Impagnatiello, Nicox Research Institute, Via Ariosto 21, Bresso 20091, Milan, Italy, firstname.lastname@example.org; email@example.com
Contributors The authors listed agreed to allow the corresponding author, FI, to correspond with the editorial office, to review the uncorrected proof copy of the manuscript and to make decisions regarding release of information in the manuscript. On behalf of all listed authors, the corresponding author certifies that neither this manuscript nor one with substantially similar content has been published or is being considered for publication elsewhere. FI has access to any data on which the manuscript is based and will provide such data on request to the editors or their assignees. FI takes public responsibility for the whole content of the manuscript. According to the definition given by the International Committee of Medical Journal Editors (ICMJE), the authors listed all qualify for authorship based on each making a substantial contribution to the intellectual content, conception and design, acquisition, analysis and interpretation of the data. Furthermore, all authors participated in drafting the manuscript as well as in its critical revision for important intellectual content. All authors contributed equally to this work.
Accepted 17 December 2011
Published Online First 18 January 2012
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.
british journal of ophtalmo