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Mei-Ling Gao, Kun-Chao Wu, Xin-Lan Lei, Wen-Li Deng, Chun-Yun Feng, Dongqing Li, Zi-Bing Jin; TLR3 mediated innate immunity is essential for retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5795.
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© ARVO (1962-2015); The Authors (2016-present)
Inflammation is considered as an important biological process in age-related macular degeneration (AMD). One component of drusen in AMD is dsRNA which activates Toll-like receptor-3 (TLR3) and induces inflammation that may cause damage associated molecular patterns (DAMPs). The purpose of this study is to investigate whether the DAMPs participate in the pathogenesis of AMD.
The dsRNA analog Poly(I:C) was employed as TLR3 activator and was transfected into photoreceptor cells. The dsDNA analog Poly(dI:dC) were used as control. Gene expression was analyzed with quantitative RT-PCR and cell viability was assessed using mitochondrial membrane potential assay and Annexin-V/PI double staining. Z-VAD and Necrostatin-1 were used to prevent cell death induced by Poly(I:C). In mouse model, Poly(I:C), Poly(dI:dC) or PBS were injected into the subretinal space. Quantitative RT-PCR and western blotting were performed to confirm the inflammation induced by Poly(I:C). Immunostaining of GFAP and Iba1were also conducted and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling was conducted to determine cell death. Fundus photo and electroretinogram were carried out.
Here we showed that Poly(I:C) activated TLR3 and mediated inflammation in a mouse photoreceptor cell line, most of which were Arrestin positive, a cone expressing gene. Poly(I:C) induced photoreceptor cell death though necrosis, but not apoptosis. After, subretinal injection of Poly(I:C), TLR3 was activated as well and induced inflammation in mouse neural retina. Moreover, muller glia cells were activated and microglia cells migrated into the out nuclear layer or out of the subretinal space, just like early or intermediate dry AMD. Poly(I:C) treatment led to significant retinal degeneration and photoreceptor cell death. On the other hand, photoreceptor function was significantly reduced after Poly(I:C) treatment.
Therefore, TLR3 mediated innate immunity may play important role in retinal degeneration and the release of intracellular DAMPs may promote inflammation that aggravate AMD progression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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