Francisco M Nadal-Nicolás1, Esther Rodriguez-Villagra2, Irene Bravo-Osuna3, Paloma Sobrado-Calvo1, Irene Molina-Martínez3, Maria Paz Villegas-Pérez1, Manuel Vidal-Sanz1, Marta Agudo-Barriuso1, Rocío Herrero-Vanrell3. 1. Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain. 2. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain, and Fundación para la Investigación-HCSC, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. 3. Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain, and Fundación para la Investigación-HCSC, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain 3Instituto Universitario.
Abstract
PURPOSE: To assess the neuroprotective effects of ketorolac administration, in solution or delivered from biodegradable microspheres, on the survival of axotomized retinal ganglion cells (RGCs). METHODS: Retinas were treated intravitreally with a single injection of tromethamine ketorolac solution and/or with ketorolac-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Ketorolac treatments were administered either 1 week before optic nerve crush (pre-ONC) or right after the ONC (simultaneous). In all cases, animals were euthanized 7 days after the ONC. As control, nonloaded microspheres or vehicle (balanced salt solution, BSS) were administered in parallel groups. All retinas were dissected as flat mounts; RGCs were immunodetected with brain-specific homeobox/POU domain protein 3A (Brn3a), and their number was automatically quantified. RESULTS: The percentage of Brn3a+RGCs was 36% to 41% in all control groups (ONC with or without BSS or nonloaded microparticles). Ketorolac solution administered pre-ONC resulted in 63% survival of RGCs, while simultaneous administration promoted a 53% survival. Ketorolac-loaded microspheres were not as efficient as ketorolac solution (43% and 42% of RGC survival pre-ONC or simultaneous, respectively). The combination of ketorolac solution and ketorolac-loaded microspheres did not have an additive effect (54% and 55% survival pre-ONC and simultaneous delivery, respectively). CONCLUSIONS: Treatment with the nonsteroidal anti-inflammatory drug ketorolac delays RGC death triggered by a traumatic axonal insult. Pretreatment seems to elicit a better output than simultaneous administration of ketorolac solution. This may be taken into account when performing procedures resulting in RGC axonal injury.
PURPOSE: To assess the neuroprotective effects of ketorolac administration, in solution or delivered from biodegradable microspheres, on the survival of axotomized retinal ganglion cells (RGCs). METHODS: Retinas were treated intravitreally with a single injection of tromethamine ketorolac solution and/or with ketorolac-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Ketorolac treatments were administered either 1 week before optic nerve crush (pre-ONC) or right after the ONC (simultaneous). In all cases, animals were euthanized 7 days after the ONC. As control, nonloaded microspheres or vehicle (balanced salt solution, BSS) were administered in parallel groups. All retinas were dissected as flat mounts; RGCs were immunodetected with brain-specific homeobox/POU domain protein 3A (Brn3a), and their number was automatically quantified. RESULTS: The percentage of Brn3a+RGCs was 36% to 41% in all control groups (ONC with or without BSS or nonloaded microparticles). Ketorolac solution administered pre-ONC resulted in 63% survival of RGCs, while simultaneous administration promoted a 53% survival. Ketorolac-loaded microspheres were not as efficient as ketorolac solution (43% and 42% of RGC survival pre-ONC or simultaneous, respectively). The combination of ketorolac solution and ketorolac-loaded microspheres did not have an additive effect (54% and 55% survival pre-ONC and simultaneous delivery, respectively). CONCLUSIONS: Treatment with the nonsteroidal anti-inflammatory drug ketorolacdelays RGC death triggered by a traumatic axonal insult. Pretreatment seems to elicit a better output than simultaneous administration of ketorolac solution. This may be taken into account when performing procedures resulting in RGC axonal injury.
Authors: Francisco M Nadal-Nicolás; Manuel Jiménez-López; Manuel Salinas-Navarro; Paloma Sobrado-Calvo; Manuel Vidal-Sanz; Marta Agudo-Barriuso Journal: J Neuroinflammation Date: 2017-11-09 Impact factor: 8.322
Authors: Alba Aragón-Navas; María J Rodrigo; David Garcia-Herranz; Teresa Martinez; Manuel Subias; Silvia Mendez; Jesús Ruberte; Judit Pampalona; Irene Bravo-Osuna; Julian Garcia-Feijoo; Luis E Pablo; Elena Garcia-Martin; Rocío Herrero-Vanrell Journal: Drug Deliv Date: 2022-12 Impact factor: 6.819