Methods: Endothelin-1 (ET-1) induced ischemia/reperfusion injury model in rabbits was used. ET-1 was injected nearby the optic nerve head (ONH) twice/week for 6 weeks. Starting on week 3, the animals received vehicle (VEH), NCX 470, LUM, or BIM (30 mu L/eye, twice daily, 6 days/week) until the end of ET-1 treatment. Intraocular pressure (IOP), ophthalmic artery resistive index (OA-RI), and electroretinogram (ERG) data were collected prior to dosing and at different time points postdosing. Reduced glutathione, 8-Hydroxy 2-deoxyguanosine, and Caspase-3 were determined in the retina of treated eyes. DNA fragmentation was determined by terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. Results: ET-1 increased IOP (VEHIOP_Baseline = 20.5 +/- 0.8 and VEHIOP_Week6 = 24.8 +/- 0.3 mmHg) and OA-RI (VEHOA-RI_Baseline = 0.36 +/- 0.02 and VEHOA-RI_Week6 = 0.55 +/- 0.01) and reduced rod/cone responses over time. Oxidative stress, inflammation, and apoptotic markers increased in ET-1-treated eyes. NCX 470 prevented IOP (NCX 470IOP_Week6 = 18.1 +/- 0.6 mmHg) and OA-RI changes (NCX 470OA-RI_Week6 = 0.33 +/- 0.01) and restored ERG amplitude leaving unaltered the respective latency; these effects were only partially demonstrated by LUM or BIM. Additionally, NCX 470 reduced oxidative stress, inflammation, and apoptosis in the retinas of treated eyes. BIM and LUM were numerically less effective on these parameters. Conclusions: NCX 470 repeated ocular dosing ameliorates ocular hemodynamics and retinal cell dysfunction caused by ischemia/reperfusion via nitric oxide- and bimatoprost-mediated mechanisms. Translational Relevance: If confirmed in clinical setting our data may open new therapeutic opportunities to reduce visual field loss in glaucoma.

NCX 470 Exerts Retinal Cell Protection and Enhances Ophthalmic Artery Blood Flow After Ischemia/Reperfusion Injury of Optic Nerve Head and Retina / Sgambellone, Silvia; Marri, Silvia; Villano, Serafina; Masini, Emanuela; Provensi, Gustavo; Bastia, Elena; Galli, Corinna; Brambilla, Stefania; Impagnatiello, Francesco; Lucarini, Laura. - In: TRANSLATIONAL VISION SCIENCE & TECHNOLOGY. - ISSN 2164-2591. - STAMPA. - 12:(2023), pp. 22.1-22.11. [10.1167/tvst.12.9.22]

NCX 470 Exerts Retinal Cell Protection and Enhances Ophthalmic Artery Blood Flow After Ischemia/Reperfusion Injury of Optic Nerve Head and Retina

Sgambellone, Silvia
;
Marri, Silvia;Villano, Serafina;Masini, Emanuela;Provensi, Gustavo;Lucarini, Laura
2023

Abstract

Methods: Endothelin-1 (ET-1) induced ischemia/reperfusion injury model in rabbits was used. ET-1 was injected nearby the optic nerve head (ONH) twice/week for 6 weeks. Starting on week 3, the animals received vehicle (VEH), NCX 470, LUM, or BIM (30 mu L/eye, twice daily, 6 days/week) until the end of ET-1 treatment. Intraocular pressure (IOP), ophthalmic artery resistive index (OA-RI), and electroretinogram (ERG) data were collected prior to dosing and at different time points postdosing. Reduced glutathione, 8-Hydroxy 2-deoxyguanosine, and Caspase-3 were determined in the retina of treated eyes. DNA fragmentation was determined by terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. Results: ET-1 increased IOP (VEHIOP_Baseline = 20.5 +/- 0.8 and VEHIOP_Week6 = 24.8 +/- 0.3 mmHg) and OA-RI (VEHOA-RI_Baseline = 0.36 +/- 0.02 and VEHOA-RI_Week6 = 0.55 +/- 0.01) and reduced rod/cone responses over time. Oxidative stress, inflammation, and apoptotic markers increased in ET-1-treated eyes. NCX 470 prevented IOP (NCX 470IOP_Week6 = 18.1 +/- 0.6 mmHg) and OA-RI changes (NCX 470OA-RI_Week6 = 0.33 +/- 0.01) and restored ERG amplitude leaving unaltered the respective latency; these effects were only partially demonstrated by LUM or BIM. Additionally, NCX 470 reduced oxidative stress, inflammation, and apoptosis in the retinas of treated eyes. BIM and LUM were numerically less effective on these parameters. Conclusions: NCX 470 repeated ocular dosing ameliorates ocular hemodynamics and retinal cell dysfunction caused by ischemia/reperfusion via nitric oxide- and bimatoprost-mediated mechanisms. Translational Relevance: If confirmed in clinical setting our data may open new therapeutic opportunities to reduce visual field loss in glaucoma.
2023
12
1
11
Goal 3: Good health and well-being
Sgambellone, Silvia; Marri, Silvia; Villano, Serafina; Masini, Emanuela; Provensi, Gustavo; Bastia, Elena; Galli, Corinna; Brambilla, Stefania; Impagnatiello, Francesco; Lucarini, Laura
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1354979
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