Effects of topical indomethacin, bromfenac and nepafenac on lipopolysaccharide-induced ocular inflammation.
OBJECTIVE
To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats.


METHODS
EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2 ) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2).


RESULTS
All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P<0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac).


CONCLUSIONS
Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism.
Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, Medical School, University of Catania, Catania, Italy.
Claudio
C
Bucolo
Giuseppina
G
Marrazzo
Chiara Bianca Maria
CB
Platania
Giovanni Luca
GL
Romano
Filippo
F
Drago
Salvatore
S
Salomone
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001577:Benzophenones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001969:Bromobenzenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects; D012166:Retinal Hemorrhage / Q000517:prevention & control*; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D001577:Benzophenones; D001969:Bromobenzenes; D008070:Lipopolysaccharides; D010648:Phenylacetates; C414203:nepafenac; C014285:amfenac; C053083:bromfenac; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007213:Indomethacin
LPS; NSAIDs; inflammation; rat; retina