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Updated: Dec 6, 2025

Efficient Dissection and Culture of Primary Mouse Retinal Pigment Epithelial Cells
Published on: February 10, 2021
IL-1/IL-1R signaling induced by all-trans-retinal contributes to complement alternative pathway activation in retinal
Xinxuan Cheng1,2,3, Danxue He1,2,3, Chunyan Liao1,2,3
1Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Eye Institute of Xiamen University, Xiamen University, Xiamen, China.
Abstract:
The underlying mechanisms of complement activation in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD) are not fully understood. Overaccumulation of all-trans-retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b-9 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin-1β production was provoked in both atRAL-treated RPE cells and microglia/macrophages. Coincubation of RPE cells with interleukin-1 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine/paracrine IL-1/IL-1R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.
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