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Ashok Kumar; Interplay of energy metabolism and retinal innate responses to infection. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2970.
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Presentation Description :
Intraocular infections such as infectious endophthalmitis remain a vision-threatening complication of ocular surgeries and trauma, often leading to blindness and visual disability. Successful treatment of these infections requires not only the elimination of the infecting pathogens but also control of the host inflammatory response, which causes retinal tissue damage, if not resolved promptly. Considering the complexity of host-pathogen interactions, we adopted the systems biology approach for modeling retinal immune defenses against pathogens to generate information for possible immunomodulatory therapies. Our recent transcriptome analysis of the bacterial (S. aureus)-infected mouse retina (Rajamani et al., Scientific Reports, 2016) revealed that the major pathways impacted in endophthalmitis include: metabolism, inflammatory/immune, antimicrobial, cell trafficking, and lipid biosynthesis. Similarly, the global metabolomics analysis confirmed that pathways involved in energy metabolism were significantly altered in bacterial endophthalmitis, particularly glycolysis and oxidative phosphorylation. As both transcriptome and metabolomics studies implicated metabolic perturbations, we investigated the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a master regulator of cellular metabolism, in retinal innate immunity. We showed that the pharmacological activation of AMPK down-regulated the inflammatory response in the retina. These findings led us to propose that AMPK is a plausible therapeutic target to promote inflammation resolution in bacterial endophthalmitis. How AMPK activation modulates energy metabolism to exert its anti-inflammatory and protective effects in intraocular infections will be discussed. Our findings may provide novel therapeutic targets for the development of anti-inflammatory therapies for endophthalmitis and other microbial infections.
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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