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Barry T. Rouse; Manipulating host metabolism to manage ocular inflammation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2971. doi: https://doi.org/.
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Presentation Description :
Chronic inflammatory lesions in the cornea, as can result from herpes simplex virus (HSV) infection, impair vision and can cause blindness. Studies on ocular HSV in mouse models have revealed that the inflammatory events involve multiple cell types and chemical mediators, some of which act to limit the extent of tissue damage. Prominent amongst the later cell types are CD4 Foxp3 positive T cells, which play a regulatory role. Accordingly, approaches to control the severity of stromal keratitis (SK) include those, which can adjust the balance of pro-inflammatory and regulatory cells (Treg) in the inflammatory lesions. We have exploited the fact that individual immune cell types may show different metabolic profiles as an approach to therapy. We show that manipulating glucose metabolism with the drug 2deoxy glucose (2DG) provides an effective way of minimizing lesions. The approach acts to minimizes the expansion and function of pro-inflammatory T cells but leaves intact the response mediated by tissue protecting Treg. Thus, modulating metabolic events shows promise as a therapeutic approach to control ocular inflammatory disease. However, as a word of caution the use of 2DG therapy when the virus is still actively replicating can result in untoward consequence such as dissemination of virus to the brain.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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