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Xiaomin Zhang, Lingjun Zhang, Hui Zheng, Hui Shao, Hong Nian, Lingling Bai, Xiaorong Li; Comparisons of Therapeutic effects of Mesenchymal Stem Cells and Dexamethasone on Recurrent Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):92.
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© ARVO (1962-2015); The Authors (2016-present)
To compare therapeutic effects of single or combined treatments of mesenchymal stem cells (MSCs) and dexamethasone (DXM) on recurrent experimental autoimmune uveitis (rEAU) and study the mechanisms of MSCs on rEAU.
rEAU was induced by injection of T cells specific to a peptide from interphotoreceptor retinoid-binding protein (IRBP) [R16, amino acid (aa) 1177-1191] in Lewis rats. Single or combined MSC and DXM treatments were applied at the disease onset. MSCs were intravenously injected for successive 3 days. Intraperitoneal DXM injections were given for 7 days, or 50 days with gradual reductions in dosing. Clinical signs of ocular inflammation were observed by slit-lamp microscope for 50 days after transfer. , subsets of T cells in the eyes, cervical draining lymph nodes and spleens were analyzed by flow cyctometry at day 10 post transfer. Functions of T cells and antigen presenting cells (APCs) in spleens were determined by - proliferation assays.
MSCs and DXM equally reduced the severity of the first attack of rEAU. . Combination of MSCs and DXM greatly improved the single treatment. After withdrawal of 7-day DXM treatment, the inflammation rebound. During the 50 days post transfer, MSC administration reduced the severity and incidence of rEAU, and protected the structure of the retina; whereas, long period of DXM treatment with gradual reduction in dosing could not reduce chronic inflammation. MSCs significantly decreased the frequency of Th17 cells in the eyes, draining lymph nodes and spleen, and had a tendency to up-regulate Tregs. Th1 cells in draining lymph nodes of MSC-treated group were also reduced. Moreover, MSCs suppressed the proliferation of R16 specific T cells and the antigen-presentation function of APCs.
Compared to DXM, an immune suppressive drug commonly used in the patients with autoimmune uveitis, MSC treatment could diminish ocular inflammation and reduce the frequency of recurrence in rat rEAU model, suggesting that MSCs could be an alternative and better therapy for the disease in clinic.
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