Abstract
Presentation Description :
Recently, cellular metabolism was identified as a critical process in the development of herpes stromal encephalitis (HSE) and herpes stromal keratitis (HSK). Specifically, the inhibition of glucose metabolism during early infection resulted in HSE; however, inhibition of glucose metabolism during the establishment of HSK reduced corneal opacity. While it is known that the inhibition of gluocose metabolism of T cells directly results in reactivation of HSV-1 from latency, it is unclear how cellular metabolism affects immune and parenchymal cells at the ocular surface. Here, using a pathogenic strain of virus (HSV-1 RE) and a non-pathogenic strain of virus (HSV-1 KOS), we show that the pathogenicity of the virus directly correlates with the metabolic signature of corneal immune and epithelial cells. Furthermore, we reveal that treating mice subconjunctivally with the antioxidant compound, ethyl pyruvate, concurrently with infection reduces glycolysis in those same cells and results in alleviation of disease without evidence of encephalitis. Therefore, this study shows how modulation of cellular metabolism using ethyl pyruvate during early HSV-1 infection can alleviate HSK.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.