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Sylvia Wandu, Guangpu Shi, Osato Ogbeifun, Lindsey Nugent, Huaibin Cai, Igal Gery; Leucine-rich repeat kinase 2 (LRRK2) deficiency diminishes the development of EAU. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1866.
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The gene leucine-rich repeat kinase 2 (LRRK2) instructs the formation of a protein, Dardarin, that plays an important role in the neural system; mutations of this gene are responsible for certain forms of Parkinson’s disease. Deficiency of LRRK2 was reported to enhance the development of experimental colitis (Liu et al. Nature Immunol., 2011). Here, we examined the effect of LRRK2 deficiency on the development of experimental autoimmune uveitis (EAU) and related immune responses.
Conventional methods were used for the induction of EAU in LRRK2 deficient mice (“KO”) and their wild type C57Bl/6 controls (“WT”) and the disease development was assessed by histological analysis on day 14 post-injection (p.i.). Draining lymph nodes were collected on day 14 p.i. and their cells were analyzed for their responsiveness to the immunizing antigen, interphotoreceptor retinal-binding protein (IRBP), by their enhanced proliferation and release of IL-17 and interferon gamma, using conventional assays. The proportion of T-regulatory cells (Treg) expressing FoxP3, was determined by flow cytometry.
Totals of 28 KO mice and 31 WT controls, in five individual experiments, were tested. Mean EAU severity was scored at 0.54+/-0.19 in KO mice and 1.75+/-0.44 in WT mice (p <0.009). Differences between the two groups in their lymphocyte responses to IRBP and release of IFN-gamma and IL-17, however, were inconsistent. Preliminary data indicate that the proportion of FoxP3 positive cells was higher in the KO mice than that in their WT controls.
Unlike the increased severity of colitis noted in LRRK2 deficient mice, EAU development was reduced in KO mice than in the WT controls. Additional studies are needed to further examine this unexpected difference.
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