IL-1? signalling bolsters chemokine-mediated inflammation in retinal photo-oxidative damage
|Collections||Collaboration across boundaries : a cross-disciplinary conference (2017)|
|Title:||IL-1? signalling bolsters chemokine-mediated inflammation in retinal photo-oxidative damage|
|Publisher:||Canberra, ACT : NECTAR, The Australian National University|
Macrophage accumulation within the injured retina exacerbates photoreceptor death in retinal degenerations including age-related macular degeneration (AMD). This is dependent upon Ccl- and Cxcl- chemokine expression by RPE and Möller cells. However, the precise signalling events that promote their expression are unclear. We investigate the role of IL-1? in modulating chemokine expression by RPE and Moller cells in photo-oxidative damage (PD). Methods: IL-1? siRNA or neutralising antibody was intravitreally injected in SD rats prior to PD. Animals were exposed to 1000lux light for 24hrs, after which retinas were collected. Expression and localisation of IL-1?, Ccl2, Cxcl1 and Cxcl10 genes were assessed via qPCR and in situ hybridisation, while immunohistochemistry (IBA1+ microglia/macrophages) and TUNEL (photoreceptor death) were used for histological analysis. Results: Following PD, elevated levels of IL-1? (P<0.05) were detected in outer retinal IBA1+ microglia, which coincided with increased expression of Ccl2, Cxcl1 and Cxcl10 (P<0.05). Neutralising IL-1? protein was found to decrease Ccl2, Cxcl1 and Cxcl10 following PD, specifically in RPE and Möller cells. Inhibiting IL-1? gene expression via targeted-siRNA significantly reduced the expression of Ccl2 and Cxcl1, though not Cxcl10. Moreover, inhibiting IL-1? with either siRNA or neutralising antibody reduced IBA1+ cell migration into the outer retina, and suppressed photoreceptor death (P<0.05).Conclusion: IL-1? signalling modulates chemokine expression by RPE and Möller cells in retinal degenerations, reducing microglia/macrophage accumulation and photoreceptor loss. Therapeutic strategies which target IL-1? may be helpful in managing excessive chemokine signalling and macrophage infiltration that contribute to retinal degenerations such as AMD.
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