Topical Treatment With Bromfenac Reduces Retinal Gliosis and Inflammation After Optic Nerve Crush.
OBJECTIVE
To study the effect of topical administration of bromfenac, a nonsteroidal anti-inflammatory drug (NSAID), on retinal gliosis and levels of prostaglandin E2 (PGE2) after complete optic nerve crush (ONC).


METHODS
Adult albino rats were divided into the following groups (n = 8 retinas/group): (1) intact, (2) intact and bromfenac treatment (twice a day during 7 days), (3) ONC (7 days), and (4) ONC (7 days) + bromfenac treatment (twice a day during 7 days). Animals from groups 3 and 4 were imaged in vivo with spectral-domain optical coherence tomography (SD-OCT) before the procedure and 15 minutes, 3, 5, or 7 days later. Retinas from all groups were analyzed by immunodetection, Western blotting, or enzyme-linked immunoabsorbent assay (ELISA).


RESULTS
Quantification of Brn3a (brain-specific homeobox/POU domain protein 3A) +RGCs (retinal ganglion cells) in cross sections showed that bromfenac treatment does not accelerate ONC-induced degeneration. Cellular retinaldehyde binding protein 1 regulation indicated that bromfenac improves retinal homeostasis in injured retinas. Spectral-domain OCT showed that the thickness of the retina and the retinal nerve fiber layer at 7 days post ONC was significantly reduced in bromfenac-treated animals when compared to untreated animals. In agreement with these data, hypertrophy of astrocytes and Müller cells and expression of glial fibrillary acidic protein and vimentin were greatly diminished by bromfenac treatment. While no changes in cyclooxygenase (COX) enzyme COX1 and COX2 expression were observed, there was a significant increase of PGE2 after ONC that was controlled by bromfenac treatment.


CONCLUSIONS
Topical administration of bromfenac is an efficient and noninvasive treatment to control the retinal gliosis and release of proinflammatory mediators that follow a massive insult to the RGC population.
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain 2Faculty of Medicine, Tor Vergata University, Rome, Italy.
Giuseppe
G
Rovere
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Francisco M
FM
Nadal-Nicolás
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Paloma
P
Sobrado-Calvo
Terapia celular y trasplante hematopoyético (IMIB-Arrixaca), Murcia, Spain.
David
D
García-Bernal
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Maria Paz
MP
Villegas-Pérez
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Manuel
M
Vidal-Sanz
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia e Instituto Murciano de Investigación Biosanitaria-Hospital Universitario Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Marta
M
Agudo-Barriuso
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001577:Benzophenones / Q000008:administration & dosage*; D015153:Blotting, Western; D001969:Bromobenzenes / Q000008:administration & dosage*; D002452:Cell Count; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D009883:Ophthalmic Solutions; D009898:Optic Disk / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009902:Optic Neuritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods; D050819:Transcription Factor Brn-3A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D001969:Bromobenzenes; D009883:Ophthalmic Solutions; D050819:Transcription Factor Brn-3A; C053083:bromfenac