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

Ethan Zhang; Joseph Ryu; Sarah R. Levi; Jin Kyun Oh; Chun Wei Hsu; Xuan Cui; Ting-Ting Lee; Nan‐Kai Wang; José Ronaldo Lima de Carvalho; Stephen H. Tsang

doi:10.1007/s00335-020-09837-1

GeneticsMammalian GenomeApr 1, 2020

Peer-reviewed journal article

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

Ethan Zhang, Joseph Ryu iD, Sarah R. Levi iD, Jin Kyun Oh iD, Chun Wei Hsu, Xuan Cui iD, Ting-Ting Lee iD, Nan‐Kai Wang iD, José Ronaldo Lima de Carvalho iD, Stephen H. Tsang iD

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.

PDF DOI