Abstract
Presentation Description :
The retinal pigment epithelium (RPE) represents the outer blood-retina barrier and is thus responsible for the maintenance of the ocular immune privilege. Therefore, it also has to display features of immune cells. We have recently found that RPE cells can express FoxP3, originally detected as a transcription factor of regulatory T cells (Tregs). While the RPE in healthy eyes of young animals is devoid of FoxP3, increasing expression is correlated with age and upregulation seen in tissue alterations like geographic atrophy and age-related macular degeneration (AMD). Moreover, FoxP3 expression is also induced under inflammatory conditions that lead to retinal destruction like in experimental uveitis. Even more exciting was our observation that, like in human T cells, FoxP3 expression can be relocated between the cytosol and the nucleus, depending on the stress stimulus impacting these cells.
We have therefore investigated the FoxP3 expression in the human RPE cell line ARPE-19 after various stress stimuli imitating infection, tissue destruction by introducing cell death or blocking ion channels and looked for the qualitative and quantitative expression of post-transcriptional FoxP3 variants like N- and C-terminally processed molecules as well as phosphorylated FoxP3 by immunofluorescence staining. In addition, we have investigated the concomitant cytokine responses of ARPE-19 cells and found increased production of VEGF, IL-6 and IL-8/CXCL8 and, depending on the stress stimulus, CXCR4 and its phosphorylated form were upregulated.
We are expecting novel insights into cellular mechanisms of the blood-retina barrier to understand and treat or prevent malfunction like in chronic uveitis and AMD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.