Doyne lecture 2016: intraocular health and the many faces of inflammation

摘要: Dogma for reasons of immune privilege including sequestration (sic) ocular antigen, lack lymphatic and competent cells in the vital tissues eye has long evaporated. Maintaining tissue cellular health to preserve vision requires active responses prevent damage respond danger. A priori must contain cells, undergo surveillance ensure homoeostasis as well an ability promote inflammation. By interrogating non-infectious uveitis compare with age-related macular degeneration (AMD), new concepts intraocular emerge. The role macrophage polarisation two disorders is a tractable start. TNF-alpha regulation pivotal role, supported via experimental evidence validated by recent trial data. Contrast this slow, insidious atrophic AMD or neovasular AMD, compelling genetic association innate immunity complement, highlights attenuate pathogenic despite known inflammasome activation. Yolk sac-derived microglia maintains health. result cell activation environmentally dependent, example, on retinal bioenergetics status, autophagy oxidative stress, alterations that skew interaction between macrophages pigment epithelium (RPE). For dead RPE eliciting VEGF secretion but exogenous IL-4 liberates anti-angiogenic sFLT-1 response. Impaired stress drives activation, increases cytotoxicity, accentuation neovascular responses, yet inflammasome-derived cytokines, such IL-18 IL-33, responses.