Fig. 7

Metabolomic profiles of optic nerves following high dose NAM given prophylactically (before the onset of HT) or as an intervention (after the onset of HT). In each case the normotensive eye (N.HT) is compared with the hypertensive eye (G.HT) from the same rat. These plots demonstrate that the metabolic profiles for high pressure eye converge on the those for nomotensive eyes following high dose NAM treatment. A–C Principal component analysis of metabolomic profiles comparing the normal and hypertensive eyes from rats with induced ocular hypertension. A No NAM treatment. B Prophylactic High NAM treatment. C Interventional high NAM treatment. D–F corresponding Volcano plots of NT vs. HT (no NAM treatment) (D), NT vs. HT (prophylactic NAM treatment) (E), and NT vs. HT (interventional NAM treatment) (F) indicating the convergence of the metabolomic profile following NAM treatment (E, F) compared with no NAM treatment (D). No significant change in metabolite profile in HT eye was seen following NAM treatment when given at a prophylactic or interventional high dose. G–I Pathway analysis (MetaboAnalyst) was performed on detected metabolites and annotated using the Rattus norvegicus KEGG library (G) Pathway analysis of NT vs. HT (no NAM treatment; Untreated). H NT vs. HT (prophylactic NAM treatment; Prophylactic). I NT vs. HT (interventional NAM treatment; Intervention). Significant fold change (^>2) are shown (red markers) for 5-ALA: 5-aminolevulinic acid; AA: arachidonic acid; ADMA: asymmetric dimethylarginine; DHAP: dihydroxyacetone phosphate F6P: Fructose-6-phosphate; G3P: glyceraldehyde-3-phosphate; GPC: glycerophosphocholine; G6P: glucose-6-phosphate; Met: methionine; O-PE: O- phosphoethanolamine; PEP: phosphoenolpyruvate. No significant fold changes are seen following prophylactic or interventional NAM at high dose (and none of the corresponding pathways are significantly enriched in these comparisons; H and I)