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.

A nonrandomized controlled study of inflammatory response between uveitic glaucoma and other refractory glaucoma following Ahmed glaucoma valve implantation / 中华实验眼科杂志

Background The aqueous flare is obvious in uveitic glaucomatous eye due to the damage of blood-aqueous barrier,especially following intraocular surgery.How to quantitatively determine the aqueous flare is important for us to understand the severity of inflammatory response.Objective This study was to assess inflammatory response following Ahmed glaucoma valve implantation in uveitic glaucomatous eye.Methods A nonrandomized controlled study was carried out under the approval of Ethic Committee of Zhongshan Ophthalmic Center of Sun Yat-sen University.Twenty-nine eyes of 29 subjects with refractory glaucoma were enrolled this hospital from October 2011 through July 2012.The patients were divided into the uveitic glaucoma group (10 eyes) and the other refractory glaucoma group (19 eyes) with the matched demography,and Ahmed glaucoma valve implantation was performed on all the eyes under the informed consent of each patient.The aqueous flare value was determined with FC-2000 flare-cell photometry and intraocular pressure (IOP) was measured with Goldmann tonometer before surgery and 1 day,3 days,1 week,2 weeks,1 month and 3 months after surgery.The outcomes were compared between the two groups,and the correlation of aqueous flare value with IOP was analyzed.Results In the uveitic glaucoma group,the aqueous flare values were 21.10 (10.50,38.58) photoparticles/ms,88.00 (23.55,168.63) photoparticles/ms and 29.90 (8.90,65.18)photoparticles/ms 1 day,3 days and 1 week after surgery,which were significantly higher than 13.53 (7.60,24.00) photoparticles/ms before surgery (all at P＜0.01).The same trend was found in the other refractory glaucoma group.In addition,the aqueous flare value was higher in the uveitic glaucoma group than that in the other refractory glaucoma group in 3 months after surgery (q=-3.445,P＜0.01).No significant differences were seen in IOP between the two groups at various time points (all at P＞0.05).Also,no significant correlations were seen between IOP and aqueous flare value in all patients at various time points (preoperation:rs =0.136,P =0.481; postoperative 1 day:rs =0.019,P =0.922 ; postoperative 3 days:rs =-0.035,P =0.858 ; postoperative 1 week:rs =0.317,P=0.094; postoperative 2 weeks:rs =0.034,P =0.861 ; postoperative 1 month:rs =-0.094,P =0.628 ; postoperative 3 months:rs =0.065,P =0.738).Conclusions FC-2000 flare-cell photometry can reflect the inflammatory reaction of the anterior chamber following Ahmed glaucoma valve implantation in various types of refractory glaucomatous eyes.The postoperative inflammatory response is more serious and lasting in uveitic glaucomatous eye.