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Enhanced apoptosis in retinal pigment epithelium under inflammatory stimuli and oxidative stress

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Abstract

Age-related macular degeneration (AMD) is a neurodegenerative disease that causes irreversible central vision loss in the elderly. Retinal pigment epithelium (RPE) has been found to be a key component in AMD pathogenesis. The Ccl2 −/− /Cx3cr1 −/− (DKO) mouse on Crb1 rd8 background is created as an AMD model, developing AMD-like retinal lesions. Our study aimed to examine RPE apoptosis in DKO mouse and human ARPE-19 cell line. DKO RPE expressed higher apoptotic proteins when compared with age-matched wild type (WT) RPE in physiological conditions. Apoptosis of primary cultured mouse RPE was evaluated under stimulation with lipopolysaccharide for inflammatory stimulation and 2,3,7,8-tetrachlorodibenzo-p-dioxin or H2O2 for oxidative stress. Compared with WT RPE, DKO RPE was more susceptible to Fas ligand (FasL)-mediated apoptosis under both inflammatory and oxidative stress, with less cell viability and higher expression of apoptotic transcripts and proteins. Decreased cell viability was also observed in ARPE-19 cells under each stimulus. Furthermore, we also investigated the anti-apoptotic effects of decoy receptor 3 (DcR3), a decoy receptor for FasL, on ARPE-19 cells under inflammatory and oxidative stress. DcR3 pre-incubated ARPE-19 cells showed decreased apoptosis, with increased cell viability and decreased expression of apoptotic transcripts and proteins under the stimuli. On the contrary, knockdown of DcR3 in ARPE-19 cells showed totally opposite results. Our study demonstrates that FasL-mediated RPE apoptosis may play a pivotal role in AMD pathogenesis.

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Acknowledgments

The National Eye Institute Intramural Research Program supported the study.

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Authors and Affiliations

  1. Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Dr., 10/10N103, NIH/NEI, Bethesda, MD, 20892-1857, USA

    Yujuan Wang, Defen Shen, Vinson M. Wang, Jingsheng Tuo & Chi-Chao Chan

  2. Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Yujuan Wang

  3. Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Cheng-Rong Yu & Ren-Xi Wang

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  1. Yujuan Wang
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Correspondence to Chi-Chao Chan.

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Wang, Y., Shen, D., Wang, V.M. et al. Enhanced apoptosis in retinal pigment epithelium under inflammatory stimuli and oxidative stress. Apoptosis 17, 1144–1155 (2012). https://doi.org/10.1007/s10495-012-0750-1

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