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Background: Age-related macular degeneration (AMD) involves complement activation; however, initiating ligands and essential arms of the complement cascade are unknown. Results: Phospholipid neoepitopes recognized by natural IgM antibodies triggered lectin pathway in RPE injury models. Conclusion: A role for neoepitopes in triggering AMD pathology was identified. Significance: Identifying macular neoepitopes and components of the complement cascade essential for pathology will aid in developing new therapeutic approaches.

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