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bioRxiv · 10.1101/826651

PKM2 ablation enhanced retinal function and survival in a preclinical model of retinitis pigmentosa

Zhang, E.·Ryu, J.·Levi, S. R.·Oh, J. K.·Hsu, C. W.·Lima de Carvalho, J. R.·Cui, X.·Yang, T.·Tsang, S. H.
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Abstract

Retinitis pigmentosa (RP) is a neurodegenerative disorder that causes irreversible vision loss in over 1.5 million individuals world-wide. In this study, we demonstrate that a metabolic reprogramming can treat degeneration in a Pde6{beta} preclinical model of RP. Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that transfers phosphate from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), promoting glucose catabolism. Ablation of PKM2 resulted in enhanced photoreceptor survival and function in Pde6{beta}-mutated mice compared with those without ablation. Electroretinogram (ERG) analyses revealed that the maximum b-wave is on average greater in Pkm2 knockout mice than in mice with Pkm2 intact. These rescue phenotypes from Pkm2 ablation in a preclinical model of RP indicate that a metabolome reprogramming may be useful in treating RP.

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Zhang, E., Ryu, J., Levi, S. R., Oh, J. K., Hsu, C. W., Lima de Carvalho, J. R., Cui, X., Yang, T., Tsang, S. H.. 2019-10-31. PKM2 ablation enhanced retinal function and survival in a preclinical model of retinitis pigmentosa. https://doi.org/10.1101/826651

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