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. 2022 Jul 15;13(7):613. doi: 10.1038/s41419-022-05074-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — Pyruvate kinase activity was measured from 2-month-old IGF-1R-WT, ^rodIgf-1r^−/− (A) and ^retIgf-1r^−/− (B) mice. Data are mean ± SEM (n = 12). Unpaired nonparametric Mann-Whitney test was used to determine the significance between these two groups. *p < 0.0001. ATP levels were measured from 2-month-old IGF-1R-WT, ^rodIgf-1r^−/− (C) and ^retIgf-1r^−/−mice (D). Data are mean ± SEM (n = 4). Unpaired nonparametric Mann-Whitney test (C) and unpaired parametric test with Welch’s correction (D) were used to determine the significance. *p < 0.05, **p < 0.01. Principal component analysis (PCA) of the samples based on 48 unique compounds demonstrated a clear separation between the tested groups (E). Steady-state level retinal metabolites were measured from 2-month-old IGF-1R-WT and ^rodIgf-1r^−/− mouse retina (F) and data were subjected to a network (G) and interaction analysis (H). Data are mean ± SEM (n = 4). One-way ANOVA with the Kruskal-Wallis test was used to determine the significance. *p < 0.05. NAD, NADH (I), NADP, and NADPH (J) were measured from 2-month-old IGF-1R-WT mice and ^rodIgf-1r^−/− mice, and NADH/NAD (K) and NADPH/NADP (L) ratios were calculated. Data are mean ± SEM (n = 9). Unpaired t test with Welch’s correction was used to determine the significance between these two groups. *p < 0.0001.