Ocular inflammatory effects of intravitreally injected tumor necrosis factor-alpha and endotoxin

Fleisher, Lloyd N.; Ferrell, J.; McGahan, M.C.

doi:10.1007/bf00915816

Cited by 59 publications

(34 citation statements)

References 27 publications

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“…TNFa and IL-1b also seem responsible for the rapid infiltration of leukocytes and protein leakage observed in lipopolysaccharide-induced uveitis in the rabbit. [1][2][3] These and other findings have made TNFa a potential target for immunotherapy in this type of disease, and the administration of anti-TNFa monoclonal antibodies has been related to a significant improvement in uveitis in some experimental models. 4 In humans, anti-TNFa antibodies have proved useful for the treatment of panuveitis associated with Behçet's disease.…”

Section: Introductionmentioning

confidence: 99%

Long-term treatment of refractory posterior uveitis with anti-TNFα (infliximab)

Benítez-del-Castillo

Martinez-de-la-Casa

Pato-Cour

et al. 2004

Eye

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Purpose To evaluate the long-term efficacy and safety of infliximab as treatment for noninfectious posterior uveitis. Methods An open-label clinical trial including seven patients (12 eyes) with posterior uveitis refractory to conventional treatment regimens with corticosteroids and at least one immunosuppressive agent. Three intravenous doses of 5 mg/kg of infliximab were administered at weeks 0, 2, and 6. Infliximab infusion was repeated in patients undergoing a relapse of uveitis after initial remission. Improvement was defined as amelioration of visual acuity or disappearance of retinal exudates and/or haemorrhages, decreased macular oedema and/or vitreous opacities. All patients were followed up for at least 36 months.

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Section: Introductionmentioning

confidence: 99%

Long-term treatment of refractory posterior uveitis with anti-TNFα (infliximab)

Benítez-del-Castillo

Martinez-de-la-Casa

Pato-Cour

et al. 2004

Eye

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“…The EIU model in rabbits is clinically and histopathologically similar to acute Environmental Health Perspectives * Vol 106, Supplement 5 * October 1998 'NO AND ONOO-IN WEITIS anterior uveitis in humans (9,10). The acute inflammation is associated with vascular and permeability changes in the anterior chamber of the eye.…”

Section: No and Onoo-in Experimental Uveitismentioning

confidence: 80%

“…To this end, animal models of uveitis have been extensively used to try to elucidate the complex cascade of events leading to uveitis. Uveitis involves the recruitment of leukocytes into the uvea and the disruption of the blood barrier, resulting in protein extravasation and cellular infiltration into the aqueous humor and anterior chamber (9,10). Studies from animal models of uveitis and human patients with uveitis implicate reactive oxygen/nitrogen radicals in this inflammatory process.…”

Section: Janice_allen@ncsuedumentioning

confidence: 99%

“…Endotoxin-induced uveitis in rabbits is induced by a single intravitreal injection of endotoxin (10 ng; Escherichia colt) into one eye of New Zealand white male rabbits (2-3 kg) and the appropriate vehicle into the contralateral eye (9,10). Temporal assessment of uveitis is monitored by direct examination of the anterior segment with a slit-lamp biomicroscope.…”

Section: No and Onoo-in Experimental Uveitismentioning

confidence: 99%

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Nitric oxide and peroxynitrite production in ocular inflammation.

Allen

Keng

Privalle

1998

Environ Health Perspect

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Recent studies have implicated nitric oxide and peroxynitrite in the pathogenesis of many diseases, such as septic shock, arthritis, lung disease, and atherosclerosis. Nitric oxide ('NO) exerts many diverse effects on vascular tone, affecting neurotransmission and cellular cytotoxicity/communication. Our laboratory and others have documented a proinflammatory role for 'NO in ocular inflammation. Uveitis, which is an inflammation of the highly vascular uveal tract in the eye, is a debilitating condition that can lead to visual impairment and blindness. It is characterized by acute, recurrent, or persistent inflammation with disruption of the blood-aqueous barrier and is accompanied by protein leakage and leukocyte infiltration into the aqueous humor and anterior chamber. Systemic injection of endotoxin into mice and rats, or intraocular injection of endotoxin into mice, rats, and rabbits induces acute uveitis, which clinically and histologically resembles acute anterior uveitis in humans. These models facilitate the study of pathogenic mechanisms that contribute to ocular inflammation. In addition to 'NO, superoxide anion radicals (02'-), and peroxynitrite (ONOO-), the products of the reaction between 'NO and 02'-, are also implicated in uveitis. The role of peroxynitrite in ocular inflammation is still largely unknown. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information critical to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic intervention(s) can be developed.

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“…Estudos em animais e humanos sugerem que TNF tem importante papel no desencadeamento e manutenção da uveíte experimental (6)(7)(8) . O papel pró-inflamatório do TNF na uveíte é sustentado pela observação de que a injeção intraocultar em coelhos induz a formação de uveíte (9,10) . Em humanos portadores de uveíte, elevados níveis de TNF foram demonstrados no humor aquoso coletado no intraoperatório (11) .…”

Section: Introductionunclassified

Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos

Rassi¹,

Rigueiro²,

Isaac³

et al. 2011

Arq. Bras. Oftalmol.

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RESUMOObjetivo: Determinar os níveis de toxicidade de duas e três aplicações intravítreas de infliximabe na retina de coelhos albinos, por meio de exames clínicos oftalmoló-gicos, eletrorretinográficos e histológicos. Métodos: Foram utilizados doze coelhos albinos divididos em dois grupos. No primeiro grupo de 10 coelhos, cada olho recebeu duas (n=10 olhos) ou três injeções (n=10 olhos) intravítreas de 2 mg de infliximabe dissolvidos em 0,06 ml de solução salina, em intervalos mensais. Um segundo grupo de dois coelhos, que serviu como grupo controle (n=4 olhos), foram submetidos a duas e três aplicações intravítreas de BSS. Noventa dias após, os coelhos foram novamente submetidos a exame oftalmológico (biomicroscopia, oftalmoscopia e tonometria), eletrorretinográfico e, após enucleados, a exame histológico. Resultados: O exame biomicroscópico e oftalmoscópico não revelou anormalidades retinianas nos olhos injetados com infliximabe e no grupo controle. Alteração histológica notada foi a presença de raros linfócitos e eosinófilos no vítreo posterior em quatro e em seis olhos submetidos a duas e três aplicações de infliximabe sem significado clínico. A única alteração clinicamente significante foi uma reação inflamatória severa com presença de exsudatos vítreos na interface vítreo retiniana e discreto edema de células ganglionares nos dois olhos de um único coelho, sem alterações no vítreo posterior. Os exames eletrorretinográficos mostraram amplitudes em média 12-13% menores daquelas obtidas antes do tratamento, contudo não houve nenhuma diferença estatisticamente significante quando comparamos as amplitudes e a latencia entre os achados electrorretinográficos pré e pós-tratamento. Conclusão: Duas e três aplicações intravítreas de infliximabe em olhos de coelhos em intervalos mensais, na dosagem de 2 mg, não provocam alterações significantes após um seguimento de noventa dias, quer no exame histológico, na eletrorretinografia e na avaliação clínica oftalmológica. Conclui-se que doses seriadas de infliximabe por via intravítrea é um procedimento seguro. Estudos clínicos em humanos devem ser realizados para melhor avaliação da segurança do seu uso no tratamento de determinadas doenças que acometem a retina e a coroide. Descritores

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Ocular inflammatory effects of intravitreally injected tumor necrosis factor-alpha and endotoxin

Cited by 59 publications

References 27 publications

Long-term treatment of refractory posterior uveitis with anti-TNFα (infliximab)

Long-term treatment of refractory posterior uveitis with anti-TNFα (infliximab)

Nitric oxide and peroxynitrite production in ocular inflammation.

Estudo de toxicidade retiniana após injeções intravítreas seriadas de infliximabe em olhos de coelhos

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