Purchase this article with an account.
Maren Hennig, Dirk Bauer, Martin Busch, Susanne Wasmuth, Karoline Walscheid, Solon Thanos, Arnd Heiligenhaus; Prophylactic Everolimus Treatment reduced the Experimental Autoimmune Uveoretinitis in Mice after Adoptive Transfer. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2767.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To study the efficacy and the action mechanism of everolimus for the treatment of experimental autoimmune uveoretinitis (EAU) induced by adoptive transfer.
EAU was induced in B10.RIII donor-mice by immunization with IRBPp161-180. Splenocytes and cells of the draining lymph nodes were isolated on day 14 after immunization. Cells were cultured for 72h with 30µg/ml IRBPp161-180. Antigenspecific uveitogenic cells were adoptively transferred to naïve B10.RIII mice. Recipient-mice were daily treated prophylactically (d-2-d14) and therapeutically (d5-d14) with everolimus (5mg/kg, oral application). The eyes were analyzed histopathologically. Lymphocyte proliferation ([3H]-thymidine test) and delayed type hypersensitivity (DTH) were measured. Th1, Th2, and Th17 cytokines were studied intraocularly (Bead-Array) and in cell-culture supernatants from splenocytes (ELISA). Additionally the presence of IRBPp161-180-specific serum-antibodies was tested (ELISA). Regulatory T-cells were studied in peripheral blood, lymph nodes, and spleen by flow-cytometry.
The EAU incidence and severity, the content of IRBPp161-180 specific serum antibodies, the DTH, the proliferation, and cytokine secretion of splenocytes were reduced in mice treated prophylactically with everolimus. The EAU incidence and severity and the content of IRBPp161-180 specific serum antibodies were not reduced by therapeutic everolimus treatment. In contrast the DTH, the proliferation of splenocytes, and the intraocular cytokine content of therapeutically treated mice were reduced. Additionally therapeutically treatment increased the frequency of CD4+CD25+Foxp3+ splenocytes compared to untreated mice.
The prophylactic treatment of mice with everolimus reduces the severity of EAU and the uveitogenic immune response. The reduced immune response in therapeutically treated mice might be associated with the induction of regulatory T-cells.
This PDF is available to Subscribers Only