Zamiri, Parisa;
(2004)
Studies of RPE as an immune privileged tissue and as the creator of immune privilege in the subretinal space.
Doctoral thesis (Ph.D), University College London.
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Abstract
The aims of this thesis were to investigate the role of the retinal pigment epithelium (RPE) in immune privilege of the subretinal space, and to determine the vulnerability of RPE to immune-mediated attack. An ex-vivo model of the RPE eyecup was formed from adult C57BL/6 with/without prior treatment with sodium iodate (SI), as well as thrombospondin-1 knockout (TSP-1KO) and rd mice, by removing the anterior segment and retina and leaving an intact monolayer of RPE together with choroid and sclera. The supernatant (SN) collected from the RPE eyecups which were cultured with serum free medium were used in T cell proliferation, ELISA and cytotoxicity assays to determine the contribution of RPE to the putative immunosuppressive microenvironment of the subretinal space. In addition, role of RPE in the presence of immune deviation, and in response to experimental autoimmune uveoretinitis was assessed. RPE in the eyecup preparation was relatively resistant to immune mediated attack by allo-sensitised T cells. RPE SN contained both latent and active TGF-b and thrombospondin, required for TGF-b activation. RPE SN also contained significant amount of somatostatin (SOM), a neuropeptide. RPE SN profoundly inhibited T cell proliferation and IFN-g production by antigen and anti-CD3 stimulated T cells in an active TGF-b and SOM dependent manner. Moreover, SN of RPE eyecup significantly inhibited IL-1b production by activated neutrophils and macrophages and diminished NK cells lysis of YAC-1 target cells. SN of RPE eyecups from SI-treated, or TSP-1KO and rd mice were deficient in their capacity to create an immunosuppressive microenvironment and lacked immune deviation to OVA antigen injected into their subretinal space. TSP-1 KO mice, unlike wild type mice, suffered a prolonged and severe uveoretinitis.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Studies of RPE as an immune privileged tissue and as the creator of immune privilege in the subretinal space. |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10101826 |
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