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Yuhong Wang; The Role of Pyruvate Kinase Regulation in Diabetic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2019;60(9):2660. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vertebrate photoreceptors, like cancer cells and cells in other tissues that rely on active growth, use a specific isoform of pyruvate kinase, PKM2. Like cancer cells, photoreceptors need increased glycolytic intermediates and NADPH for the anabolic process. We found evidence that both the metabolic and transcriptional regulatory functions of PKM2 influence photoreceptor structure, function, and viability. PKM2 activation has recently been shown to protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction. In this study, we examined the role of PKM2 in a mouse model of diabetic retinopathy.
Methods: We examined the expression of PKM2 and Pde6β, and tested the visual function using electroretinography in 10-week-old diabetic db/db (BKS.Cg-Dock7m+/+ Leprdb/J) and age-matched, non–diabetic control (C57BLKS/J) mice. Pyruvate kinase (PK) activity and TUNEL staining were also performed on diabetic and control mouse retinas.
Results: We found reduced expression levels of PKM2 and Pde6β, and significantly reduced rod function in diabetic mouse retinas compared with controls. We showed previously that PKM2 regulates the expression of Pde6β, and in this study reduced PKM2 expression in diabetes may decrease the expression of Pde6β that affects the rod function. Lower levels of PK activity enhance anabolic activity and inhibit oxidative phosphorylation (OxPhos). Our studies show increased PK activity in diabetic mouse retinas suggesting an increased OxPhos, and perhaps a decreased anabolic activity. Consistent with this idea, we found increased cell death in diabetic mouse retinas compared to control retinas.
Conclusions: Our findings clearly demonstrate that PKM2 has a role in diabetic retinopathy. Our studies suggest that PKM2 may have therapeutic potential in the treatment of ocular diseases associated with loss of visual function.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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