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

• Published in: Apoptosis (London) Vol. 17; no. 11; pp. 1144 - 1155
• Main Authors: Wang, Yujuan, Shen, Defen, Wang, Vinson M., Yu, Cheng-Rong, Wang, Ren-Xi, Tuo, Jingsheng, Chan, Chi-Chao
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-11-2012; Springer Nature B.V
• Subjects: Animals; Apoptosis - drug effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Cells, Cultured; Gene Knockdown Techniques; Humans; Hydrogen peroxide; Inflammation - pathology; Lipopolysaccharides - pharmacology; Macular degeneration; Mice; Mice, Knockout; Microscopy, Fluorescence; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Oncology; Original Paper; Oxidative stress; Oxidative Stress - drug effects; Polychlorinated Dibenzodioxins - pharmacology; Receptors, Tumor Necrosis Factor, Member 6b - metabolism; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; RNA, Small Interfering - metabolism; Virology; Retinal pigment epithelium (RPE); Oxidative stress; Inflammation; Fas ligand (FasL); Apoptosis; Decoy receptor 3 (DcR3)
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-012-0750-1

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
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/
−
/Cx3cr1
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/
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(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 H
2
O
2
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.