RESUMO
PURPOSE: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1ß (IL-1ß), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation. MATERIALS AND METHODS: We delivered adeno-associated virus (AAV) vectors expressing IL-1ß, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function. RESULTS: We found that IL-1ß had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1ß resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1ß was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1ß was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1ß in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1ß alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1ß or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects. CONCLUSIONS: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1ß is the most pathogenic when it is continuously expressed in the eye.
Assuntos
Citocinas/genética , Endoftalmite/genética , Regulação da Expressão Gênica , RNA/genética , Animais , Citocinas/biossíntese , Modelos Animais de Doenças , Endoftalmite/metabolismo , Endoftalmite/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Artéria Retiniana/metabolismo , Artéria Retiniana/patologia , Tomografia de Coerência ÓpticaRESUMO
A case of fibrosarcoma of the kidney is presented. Clinical and radiologic features are discussed. The arteriographic features of this tumor are indistinguishable from adenocarcinoma of the kidney. Microscopically, this tumor may be confused easily with leiomyoma or leiomyosarcoma, Special staining techniques with van Gieson and Mallory trichrome stains and electron microscopy help establish diagnosis.