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Pavan S Angadi, Shameka J Shelby, David N Zacks; IL-6 response to Edn2 stimulation in Müller cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1107.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal detachment results in the death of photoreceptors. The separation of the neurosensory retina from the retinal pigment epithelium (RPE) is both medically and surgically managed; however, significant vision loss is often seen, primarily due to the apoptotic death of the photoreceptor cells. During retina-RPE separation there are multiple molecules that are up regulated in the retina. Our lab has previously shown increased levels of Interleukin-6 (IL-6), Endothelin 2 (Edn2), and Endothelin Receptor B (EdnRB). The purpose of this study is to test the hypothesis that the release of Edn2 in the retina causes an increase in expression of IL-6, an anti-apoptotic cytokine, from Müller cells.
Retinal detachments were created in Brown Norway rats according to existing protocols, and retinas harvested at 1, 3, and 7 days post separation. Rats with attached retinas served as controls. Whole cell RNA was obtained from the retinas and assayed for transcript expression via PCR. ImM10 cells, an immortalized line of Müller cells, were used to test Müller cell specific response. Transcript levels were obtained following incubation of the cells in hypoxic conditions (our simulation of retinal detachment in cell culture), addition of mature Edn2, and both hypoxia and Edn2 addition across multiple time points.
Transcript levels of IL-6 and Edn2 peak at day 1 post detachment and gradually decrease over time in detached rat retinas. There was no change in expression of EdnRB. In ImM10 cells, transcript expression of IL-6 is increased in the presence of hypoxia, as well as in the presence of Edn2 over multiple time points. IL6 expression is further upregulated in the presence of both hypoxia and Edn2 simultaneously.
IL-6 and Edn2 expression increases following retina-RPE separation. Addition of exogenous Edn2 to Müller cells, leads to an increase in IL-6 transcript levels over untreated and hypoxic cells only. In addition, higher IL6 expression levels occurred under conditions of combined Edn2 and hypoxia. This information is the basis for further studies to understand the molecular mechanism behind Edn2 effect on an IL-6 protective response.
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