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Samuel JH Hinshaw, Osato Ogbeifun, Guangpu Shi, Igal Gery; Effects of digoxin on experimental autoimmune uveitis (EAU) development and the mouse retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1869.
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Digoxin, a major agent for the treatment of heart disease, was recently reported to inhibit the development of experimental autoimmune encephalomyelitis (EAE) (Huh, et. al., Nature, 2011). Here, we determined the immunosuppressive property of digoxin on the development of EAU, a model of uveitis in humans
B10.A mice immunized with an emulsion of interphotoreceptor retinoid-binding protein (IRBP) in CFA were treated daily (i.p) with different doses of digoxin or DMSO (vehicle control) for 14 days. On day 14 post immunization, histological examination was performed. Additionally, lymph nodes and spleens cells were cultured with IRBP to determine proliferative response and cytokine release levels. To investigate the degenerative effect of digoxin on the retina without EAU, wild-type mice (FVB/N x B.10A) F1 were treated daily (i.p) with digoxin for 13 days. Histological analysis was performed on the eyes of the mice on days 2, 4, 6, and 13.
Histological analysis of the eyes showed that the treatment of mice with digoxin inhibited the development of EAU. Proliferative response assays also showed inhibition of cellular response from splenocytes and lymph node cells, as well as diminished levels of cytokines IFN-γ and IL-17, as compared to controls. Importantly, severe retinal degeneration in digoxin-treated mice was evident via histological analysis as early as day 4, with thinning across all layers of the retina, impacting the photoreceptor layer the most.
Treatment with digoxin inhibited development of EAU in mice. However, it remains unclear whether alleviation of EAU is caused by direct action of digoxin with RORγt, or merely due to antigen loss from retinal degeneration. Regardless, the use of digoxin in humans cannot be recommended due to its strong cytotoxic properties; however, analogues may exist that retain immunosuppressive effects without such cytotoxic properties.
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