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A. Hong, P.B. Liton, C. Luna, P. Gonzalez, D.L. Epstein; Induction of the Interleukin–6 (IL–6) Gene Promoter in the Trabecular Meshwork (TM) After Mechanical Stress: Potential Implications for Aqueous Humor Outflow Modulation and Glaucoma Pathophysiology . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5149.
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Purpose: Interleukin–6 is thought to play a role in the modulation of vascular permeability as well as in the pathogenesis of several chronic disorders, including atherosclerosis and Alzheimer's disease. Here we investigated whether TM mechanical stress can induce IL–6 and studied the effects of this cytokine on outflow pathway function. Methods: A recombinant adenovirus with a 464 nt fragment of the human IL–6 gene promoter driving the expression of the secreted reporter gene SEAP was perfused into three pairs of anterior segments from porcine eyes. One eye of each pair was subjected to mechanical stress by oscillating the flow between 2µL/min (15 min) and 25 µL/min (1 min). Induction of the IL–6 promoter was measured by analyzing the amount of SEAP released to the effluent. A second adenovirus expressing LacZ under the IL–6 promoter fragment was used to analyze the site of expression of IL–6. To test the effects of IL–6 on outflow facility, porcine anterior segments were injected through the cornea with a volume of 50 µL containing either 500 ng of human IL–6 or PBS, and changes in outflow facility were monitored. Results: Mechanical stress induced a statistically significant four–fold increase in the production of SEAP driven by the IL–6 promoter with respect to nonstressed controls. LacZ expression driven by the IL–6 promoter fragment was observed preferentially in the TM. Injection of IL–6 in perfused porcine anterior segments resulted in a 40% increase in outflow facility when compared to contralateral controls. Conclusions: Given the known role of IL–6 on vascular permeability and the observed effects on outflow facility, the induction of the IL–6 promoter in TM cells after mechanical stress indicates that this cytokine could play a role in homeostatic modulation of aqueous humor flow though the TM. In addition, given the pathologic effects of IL–6 in the vascular and central nervous systems, prolonged exposure of the TM to this cytokine as a result of chronic mechanical stress could potentially contribute to the pathological alteration of the TM associated with glaucoma.
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