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Francisco M. Nadal-Nicolás, Esther Rodriguez-Villagra, Irene Bravo-Osuna, Paloma Sobrado-Calvo, Irene Molina-Martínez, Maria Paz Villegas-Pérez, Manuel Vidal-Sanz, Marta Agudo-Barriuso, Rocío Herrero-Vanrell; Ketorolac Administration Attenuates Retinal Ganglion Cell Death After Axonal Injury. Invest. Ophthalmol. Vis. Sci. 2016;57(3):1183-1192. doi: 10.1167/iovs.15-18213.
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To assess the neuroprotective effects of ketorolac administration, in solution or delivered from biodegradable microspheres, on the survival of axotomized retinal ganglion cells (RGCs).
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.
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).
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.
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