Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis.

PURPOSE: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1beta), prostaglandin E2 (PGE2), and myeloperoxidase (MPO) in rabbits with endotoxin-induced experimental uveitis. METHODS: Twenty four New Zealand white rabbits were divided into four groups (n=6 each): control (CG), morphine (MG), naloxone (NG), and morphine-naloxone (MNG) groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 µg of lipopolysaccharide (LPS) endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge) and laser flaremetry were performed before (baseline), and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. RESULTS: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P<0.05). Significant differences in PGE2 levels were observed between the MG and NMG groups (P<0.05). A trend toward increased MPO activity was observed in response to uveitis induction; however, this trend did not reach statistical significance (P>0.05). CONCLUSIONS: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.

Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis / Efeitos da morfina na expressão de citocinas e de mediadores inflamatórios em coelhos com uveítes experimental induzida por endotoxina

ABSTRACT Purpose: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1beta), prostaglandin E2 (PGE2), and myeloperoxidase (MPO) in rabbits with endotoxin-induced experimental uveitis. Methods: Twenty four New Zealand white rabbits were divided into four groups (n=6 each): control (CG), morphine (MG), naloxone (NG), and morphine-naloxone (MNG) groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 µg of lipopolysaccharide (LPS) endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge) and laser flaremetry were performed before (baseline), and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. Results: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P<0.05). Significant differences in PGE2 levels were observed between the MG and NMG groups (P<0.05). A trend toward increased MPO activity was observed in response to uveitis induction; however, this trend did not reach statistical significance (P>0.05). Conclusions: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.

RESUMO Objetivo: Estudaram-se os efeitos da instilação de morfina 1% sobre parâmetros clínicos, turbidez do humor aquoso e expressão de fator de necrose tumoral alfa (TNF-alfa), de interleucina-1 beta (IL-1beta), de prostaglandina E2 (PGE2) e de mieloperoxidase (MPO), em olhos de coelhos com uveíte induzida por endotoxina. Material e Métodos: Vinte e quatro coelhos da raça Nova Zelândia Branco foram distribuídos em quatro grupos (n=6, em cada): grupo controle (GC), morfina (GM), naloxona (GN) e morfina-naloxona (GMN). Sob anestesia dissociativa, injetou-se 0,1 mL de solução contendo 0,2 µg de lipossacarídeo (LPS) endotóxico da parede celular de Salmonella typhimurium na câmara vítrea. Realizou-se avaliação clínica (hiperemia conjuntival, quemose, blefaroespasmo e secreção ocular) e a flaremetria a “laser” antes (basal) e após 10 e 20 horas da indução da uveíte. No final, os coelhos foram submetidos à eutanásia e os olhos com uveíte foram enucleados para a quantificação dos níveis de TNF-alfa, IL-1 beta, PGE2 e MPO. Diferenças foram consideradas significativas quando p<0,05. Resultados: Os grupos da pesquisa não diferiram quanto aos parâmetros clínicos e os valores de “flare”. Observou-se elevação significativa nos níveis de TNF-alfa e de IL-1 beta, comparativamente ao basal, nos grupos GC, GM, GN e GMN (p<0,05). Valores de PGE2 variaram entre os grupos GM e GNM (p<0,05). A atividade de MPO aumentou após a indução da uveíte, porém, sem significância estatística (p>0,05). Conclusões: A morfina não atuou sobre parâmetros clínicos, “flare” e expressão dos mediadores inflamatórios estudados, quando instilada em olhos de coelhos com uveíte induzida por injeção intravítrea de LPS.

Intraocular pressure, specular microscopy, and prostaglandin E2 concentration in dogs with mature and hypermature cataract.

This study aimed to evaluate and correlate intraocular pressure (IOP), endothelial cell density (CD), and hexagonality (HEX), and the aqueous humor prostaglandin E2 (PGE2 ) concentration in dogs with mature (MG, n = 8) and hypermature (HG, n = 8) cataracts. Eight laboratory beagles with no ocular abnormalities were included as a control group (CG). The IOP was measured using a digital applanation tonometer. Noncontact specular microscopy was used to evaluate CD and HEX. Samples of aqueous humor were used to determine prostaglandin E2 concentration using enzyme-linked immunoassay. Data were compared by anova and Bonferroni's multiple comparison test, and possible correlations among the PGE2 aqueous concentration and corneal endothelium cell parameters were assessed by Person's test (P < 0.05). Average values of IOP (P = 0.45) and CD (P = 0.39) were not significantly different between MG, HM, and CG. Average values of HEX were lower, and PGE2 concentration was increased in the MG and HG in comparison with CG (P < 0.05); however, such parameters did not change significantly between MG and HG (P > 0.05). PGE2 values did not correlate with IOP, CD, and HEX in any group (P > 0.05). Although there were a small number of dogs studied, our results demonstrated that cataract progression from mature to hypermature did not have a significant change in PGE2 aqueous concentration, IOP, corneal endothelial cell count, or morphology. In addition, PGE2 concentration was not correlated with parameters of the corneal endothelium or IOP in dogs with mature or hypermature cataracts.