Open AccessPKM2 ablation enhanced retinal function and survival in a preclinical model of retinitis pigmentosa
Author(s) -
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
Publication year - 2020
Publication title -
mammalian genome
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.186
H-Index - 99
eISSN - 1432-1777
pISSN - 0938-8990
DOI - 10.1007/s00335-020-09837-1
Subject(s) - retinitis pigmentosa , biology , pkm2 , retinal degeneration , retinal , metabolome , erg , electroretinography , genetics , cancer research , pyruvate kinase , bioinformatics , metabolomics , glycolysis , endocrinology , biochemistry , metabolism
Retinitis pigmentosa (RP) is a neurodegenerative disorder that causes irreversible vision loss in over 1.5 million individuals world-wide. The genetic heterogeneity of RP necessitates a broad therapy that is able to provide treatment in a gene- and mutation- non-specific manner. In this study, we identify the therapeutic benefits of metabolic reprogramming by targeting pyruvate kinase M2 (PKM2) in a Pde6β preclinical model of RP. The genetic contributions of PKM2 inhibition in retinal degeneration were evaluated through histology and electroretinogram (ERG) followed by a statistical analysis using a linear regression model. Notably, PKM2 ablation resulted in thicker retinal layers in Pde6β-mutated mice as compared to the controls, suggesting greater photoreceptor survival. Consistent with these anatomical findings, ERG analyses revealed that the maximum b-wave is on average greater in Pkm2 knockout mice than in mice with intact Pkm2, indicating enhanced photoreceptor function. These rescue phenotypes from Pkm2 ablation in a preclinical model of RP indicate that a metabolome reprogramming may be useful in treating RP.