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K. Lucas, J. Stein-Streilein; Role of Neuropeptides in the Loss of Immune Privilege After RLB. Invest. Ophthalmol. Vis. Sci. 2010;51(13):841.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular immune privilege, in part, is mediated by the development of immune responses that lack inflammatory aspects. Here we examined the effect of retinal laser burn (RLB) on the ability of RPE cell to induce T-reg cells. We also assayed the possible role of the neuroinflammatory molecule, Substance P, as mediating the loss of immune privilege after RLB.
RLB was performed by delivering 4 laser spots to the right eye of mice. To test if immune privilege mechanisms were intact in the retina, the ipsilateral and contralateral eyes were removed from experimental or control mice. The RPE containing posterior part of the eye (excluding the neural retina) was used as an eyecup. OT1 T-cells were incubated with eyecups for 48h. T cells were collected and analyzed by flow cytometry for FoxP3 expression. In other studies, Anterior Chamber Associated Immune Deviation (ACAID) was induced in C57BL/6 or Substance P KO. Additionally, the substance P antagonist, Spantide I, was injected into the anterior chamber with OVA after RLB treatment or not.
RPE eyecups from untreated mice were able to induce primed OT-1 cells to express FoxP3 while ipsilateral eyecups from the RLB mice had fewer Foxp3 expressing cells. Eyecups from the contralateral eye had similar amounts of FoxP3+ cells as control. Substance P KO mice as well as wild-type mice treated with Spantide I did not lose ACAID after RLB treatment.
Previous data from our laboratory suggest that the ocular immunosuppressive environment of both eyes is altered after RLB treatment, however only the burned eye lost its ability to modulate primed T cells to become T reg cells. Thus, we conclude that the inflammation caused by RLB correlated with the abrogation of immune privilege in the retina. To investigate possible mechanisms in the loss of immune privilege we examined the proinflammatory neuropeptide, Substance P. We find that antagonizing or knocking out Substance P restored the ability to induce ACAID in mice that received RLB. Thus suggesting that Substance P, in part, is a major factor involved in the loss ACAID in the contralateral eye after RLB treatment.This work was supported by grants to KL: NIH F32 EY018983; JSS: DOD W81XWH and NIH EY11983.
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