title: Ketorolac Administration Attenuates Retinal Ganglion Cell Death After Axonal Injury.
abstract: OBJECTIVE
  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.
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Nadal-Nicolás
authors.affiliation: 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.
authors.forename: Esther
authors.initials: E
authors.lastname: Rodriguez-Villagra
authors.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Bravo-Osuna
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Sobrado-Calvo
authors.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Molina-Martínez
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain.
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Villegas-Pérez
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: Instituto Murciano de Investigación Biosanitaria-Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA) and Departamento de Oftalmología, Universidad de Murcia, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
authors.affiliation: 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.
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero-Vanrell
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D019771:Axotomy / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D020910:Ketorolac / Q000008:administration & dosage*; D008863:Microspheres; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D016861:Cyclooxygenase Inhibitors; D020910:Ketorolac