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Francesco Impagnatiello, Barbara Giambene, Cecilia Lanzi, Alessandro Pini, Teresa Somma, Elena Bastia, Ennio Ongini, Ugo Menchini, Fernando Galassi, Emanuela Masini; The Nitric Oxide (no)-donating Triamcinolone Acetonide, NCX 434, Does Not Increase Intraocular Pressure and Reduces Endothelin-1-induced Biochemical and Functional Changes In The Rabbit Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6065.
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© ARVO (1962-2015); The Authors (2016-present)
NCX 434 is a novel nitric oxide (NO)-donating triamcinolone acetonide (TA) with low liability to increase intraocular pressure (IOP). It also demonstrated to enhance oxygen saturation in non-human primate optic nerve head (ONH). We compared the effects of intravitreal (IVT) administration of NCX 434 and TA at equimolar doses on IOP, retinal function and retrobulbar haemodymamics in the endothelin-1 (ET-1)-induced ONH ischemia/reperfusion rabbit model. Biochemical changes were also assessed in aqueous humour and in retinal biopsies.
IOP and resistivity index of ophthalmic artery (RI-OA) were recorded by means of TonoPen and ecocolorDoppler, respectively. Retinal function was assessed using photopic electroretinography (ERG). Cytokine expression and oxidative stress markers were evaluated with immunoassay techniques.
ET-1 did not change IOP and RI-OA, but decreased photopic ERG amplitude over time. TA increased IOP while NCX 434 did not (Vehicle= 13.6±1.3, NCX 434= 16.9±2.2, TA= 20.9±1.9 mmHg*, p<0.05 vs. vehicle) 4-week post IVT treatment. RI-OA was higher following TA than after NCX 434 (Vehicle= 0.44±0.03; NCX 434= 0.47±0.02; TA= 0.60±0.04 *, p<0.05 vs. vehicle) 4-week post IVT treatment. Both NCX 434 and TA reversed ERG amplitude decrease (Vehicle=62.1±6.7; NCX 434= 149.7±7.2*; TA=131.4±9.1 uV*, p<0.05 vs. vehicle). NCX 434 also reduced oxidative stress markers, caspase-3 activity and nitrotyrosine formation in retinal tissue as well as IL6 and TNFα in aqueous humor more effectively than TA.
The IVT administration of NCX 434 attenuates the effects of ischemia/reperfusion damage to ONH and retina without increasing IOP. This compound is an interesting new development opportunity for the treatment of retinal and ONH diseases.
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