| In vivo, murine glial cells of Muller have been shown to differentially respond via the upregulation of glial fibrillary acidic protein (GFAP) to either nonspecific or virus induced inflammation. In view of this fact, the studies reported in this thesis focussed on the potential of Muller cells to participate in intraretinal immune or antiviral responses either by the production and release of soluble mediators or by the upregulation of surface molecules known to be important in either antigen presentation or other cell-cell interactions. The cytokines that were chosen for study were the Type I interferons, potent antivirals, and the proinflammatory mediators TNF{dollar}alpha{dollar} and IL-6. The surface molecules that were assessed were MHC Class I and Class II, as well as ICAM-1. These studies demonstrated that cultured retinal glial cells transcribe and translate IL-6 and TNF{dollar}alpha{dollar} under standard culture conditions and the mRNA levels of these mediators can be upregulated rapidly after exposure to either IFN{dollar}gamma{dollar} or virus. Transcription of the Type I interferons can be induced by exposure to HSV-1. Using the murine model of herpetic retinitis and a semi-quantitative RT-PCR assay, demonstrated increased cytokine transcript levels in retinas isolated from mice which were injected with HSV-1 into the anterior chamber of the eye as compared with controls. In situ hybridization results confirm that one source of the Type I interferons in the retina is the retinal glial cell. Using retinal glial cell cultures that were normally negative for MHC Class I and Class II, and expressing low levels of ICAM-1, we demonstrated that these surface markers can be upregulated in response to IFN{dollar}gamma{dollar}. Taken together, these results support the role of Muller cells as participants in intraocular immune and inflammatory responses. |
