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Deborah Y. Chong, Christopher S. Boehlke, Qiong-Duan Zheng, Linda Zhang, Ying Han, David N. Zacks; Interleukin-6 as a Photoreceptor Neuroprotectant in an Experimental Model of Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2008;49(7):3193-3200. doi: 10.1167/iovs.07-1641.
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purpose. To test the hypothesis that interleukin (IL)-6 prevents photoreceptor cell death during periods of retinal separation from the retinal pigment epithelium (RPE).
methods. Retinal-RPE separation was created in wild-type C57BL mice, IL-6−/− mice, and Brown Norway rats by subretinal injection of 1% hyaluronic acid. In some animals, anti-IL-6 neutralizing antibody (NAB) or exogenous IL-6 was administered into the subretinal space at the time of separation or at specified times afterward. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed 3 days after separation to detect apoptotic photoreceptors. Photoreceptor cell counts were performed after 1 and 2 months.
results. Loss of IL-6 function through genetic ablation (IL-6−/− mice) or injection of anti-IL-6 NAB resulted in significantly increased levels of TUNEL-positive staining 3 days after retinal-RPE separation. One month after separation, outer nuclear layer (ONL) cell counts were significantly lower in IL-6−/− mice or in animals injected with anti-IL-6 NAB than in controls. Gain of IL-6 function through the addition of exogenous IL-6 resulted in significantly increased ONL counts at 1 month but not at 2 months. Reinjection of IL-6 at 1 month led to continued preservation of ONL counts compared with controls. A window of opportunity for treatment was detected because delaying injection of exogenous IL-6 to 2 weeks after retinal-RPE separation still resulted in significantly greater ONL cell counts compared with controls.
conclusions. IL-6 may serve as a photoreceptor neuroprotectant in the setting of retinal-RPE separation.
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