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Lee Kiang, Bing X. Ross, Jingyu Yao, Sumathi Shanmugam, Chris A. Andrews, Sean Hansen, Cagri G. Besirli, David N. Zacks, Steven F. Abcouwer; Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2018;59(8):3767-3778. doi: https://doi.org/10.1167/iovs.18-24489.
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Retinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon.
Multiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD.
Twenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina.
The findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.
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