Research Article Responses of Multipotent Retinal Stem Cells to IL-1, IL-18, or IL-17 Shida Chen, 1,2 Defen Shen, 1 Nicholas A. Popp, 1 Alexander J. Ogilvy, 3 Jingsheng Tuo, 1 Mones Abu-Asab, 3 Ting Xie, 4,5 and Chi-Chao Chan 1 1 Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA 2 Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China 3 Histology Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA 4 Stowers Institute for Medical Research, Kansas City, MO 64110, USA 5 Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA Correspondence should be addressed to Chi-Chao Chan; chanc@nei.nih.gov Received 29 March 2015; Accepted 14 July 2015 Academic Editor: Naoshi Kondo Copyright © 2015 Shida Chen et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. To investigate how multipotent retinal stem cells (RSCs) isolated from mice respond to the proinfammatory signaling molecules, IL-1, IL-18, and IL-17A. Materials and Methods. RSCs were cultured in a specifc culture medium and were treated with these cytokines. Cell viability was detected by MTT assay; ultrastructure was evaluated by transmission electron microscopy; expression of IL-17rc and proapoptotic proteins was detected by immunocytochemistry and expression of Il-6 and Il-17a was detected by quantitative RT-PCR. As a comparison, primary mouse retinal pigment epithelium (RPE) cells were also treated with IL-1, IL-18, or IL-17A and analyzed for the expression of Il-6 and Il-17rc. Results. Treatment with IL-1, IL-18, or IL-17A decreased RSC viability in a dose-dependent fashion and led to damage in cellular ultrastructure including pyroptotic and/or necroptotic cells. IL-1 and IL-18 could induce proapoptotic protein expression. All treatments induced signifcantly higher expression of Il-6 and Il-17rc in both cells. However, neither IL-1 nor IL-18 could induce Il-17a expression in RSCs. Conclusions. IL-1, IL-18, and IL-17A induce retinal cell death via pyroptosis/necroptosis and apoptosis. Tey also provoke proinfammatory responses in RSCs. Tough IL-1 and IL-18 could not induce Il-17a expression in RSCs, they both increase Il-17rc expression, which may mediate the efect of Il-17a. 1. Introduction Age-related macular degeneration (AMD) is a progressive disease characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptor atrophy in the macula [1, 2]. Infammation, particularly innate immunity, is impli- cated in AMD pathogenesis [3]. Recently, the infammasome, a multimeric protein consisting of nod-like receptor (NLR), apoptosis-associated speck-like domain contains a caspase- recruitment domain (ASC), and pro-caspase-1 plays a central role in innate immunity and has been implicated in the pathogenesis of AMD [4, 5]. Activation of the NLRP3 infam- masome results in caspase-1 cleaving pro-IL-1 and pro-IL- 18 into their mature proinfammatory forms in macrophages and RPE cells [5, 6]. However, the direct efect of IL-1 and IL-18 on other retinal cells has not been well studied. In combination with IL-23, IL-1 or IL-18 can induce interleukin-17A (IL-17A) production by T17 cells,  T cells, and iNKT cells [7–10]. Growing evidence has implicated IL- 17A involvement in AMD pathogenesis. Higher levels of IL- 17A are found in the serum and macular tissues of the AMD patients when compared to age-matched controls [11, 12]. In vitro, IL-17A is cytotoxic to ARPE-19 cells, characterized by the accumulation of cytoplasmic lipids, autophagosome formation, and the presence of cleaved caspase-9 and cleaved caspase-3 [12]. IL-17RC, a member of IL-17R family and the primary receptor for IL-17A, is highly expressed in AMD macular tissues and in ARPE-19 cells [12]. In a study of Hindawi Publishing Corporation Journal of Ophthalmology Volume 2015, Article ID 369312, 9 pages http://dx.doi.org/10.1155/2015/369312