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Heping Xu, Mei Chen; Retinal Inflammation To Sterile Cell Death. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2917.
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Sterile inflammation, an inflammatory response to non-infectious pathogens, underlies the pathogenesis of a number of retinal diseases including autoimmune uveoretinitis, retinal ischemic injuries, diabetic retinopathy, and age-related macular degeneration. Although extensive studies have been carried out in the context of retinal autoimmune diseases, little is known on how retinal immune system responds to de novo non-infectious pathogens. In this study, we investigated retinal immune response to sterile cell death.
Adult C57BL/6 mice were injected intravitreally with 0.75 uM paraquat. Retinal changes were monitored clinically with topic endoscopic fundus examination (TEFI). At different days post-injection (p.i.), mice were sacrificed and eyes collected for histological investigations by light-, confocal- and electron microscopy, as well as for molecular investigation by real-time RT-PCR.
Twenty-four hours after paraquat injection, many propidium iodide positive necrotic cells were detected in the retina. Retinal oedema was observed by TEFI within 1-2 days p.i., and after one week, retinal degeneration became evident. Necrotic cell death was further confirmed by transmission electron microscopy. Microglial activation occurred as early as 12 h p.i., followed by neutrophil infiltration at 2 days p.i. The number of infiltrating neutrophils increased as the disease progressed; however, the majority of the cells were confined in the inner retina. In contrast, activated macrophages/microglia were observed throughout different layers of the retina and many of the cells exhibited multiple intracellular inclusions. Following paraquat injection, the expression of IL-1β, Nlrp3 and caspase-1 increased significantly in the retina. The treatment, however, did not affect the expression of complement C3, C4, and factor B, or the deposition of C3d in the retina.
Necrotic cell death in the retina induces an acute inflammatory response characterised by neutrophil and macrophage infiltration. Nlrp3 inflammasome may play an important role in necrotic cell death-mediated retinal inflammation.
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