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Marta Agudo, Francisco M. Nadal-Nicolas, Paloma Sobrado-Calvo, Manuel Diaz-LLopis, Manuel Vidal-Sanz, Jose-Luis Mullor; Co-Relation Between Transcriptomic And Metabolomic Changes In The Axotomized Adult Rat Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):781.
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To analyze the alterations in retinal metabolites induced by intraorbital optic nerve crush (IONC) and to link them with the transcriptome regulation triggered by the same injury.
IONC was performed in the left optic nerve of 20 adult female Sprague Dawley rats and 24 hours or 14 days later, the left retinas (n=10 per time point) were fresh extracted and immediately frozen. As control, both retinas of 5 untouched animals were processed likewise. Metabolite profiling was done by Metabolon Inc. (USA). Data of the temporal transcriptome regulation were taken from Agudo et al., Mol Vis 14:1050-63 (2008). Enrichment analyses of the altered metabolites and their link with the transcriptome changes were done using the MetacoreTM (Thomson Reuters) data analysis suite. Only significantly altered pathways or networks were considered. Custom pathway maps were done using curated interactions with MapEditorTM (Thomson Reuters).
Out of the 195 identified metabolites, 12 were regulated 24 h post-IONC, 27 at 14 days post-IONC and 35 showed a different regulation between both experimental groups. These metabolites belonged to two main superpathways: carbohydrates and aminoacids. Enrichment analyses showed that the glucose and aminoacid metabolism was significantly regulated (pEASE values: 1.075E-06 and 6.49E-05, respectively). Comparison of metabolomic and transcriptomic changes showed that several deregulated genes could explain the alterations in the metabolite concentration, including genes codifying for enzymes involved in the metabolism of glucose, fructose and the pentose phosphate pathways and in the metabolism of arginine, alanine and cysteine as well as in the initiation of translation. Custom signaling maps were generated to elucidate the functional links among them.
Our data show for the first time that axonal damage in the central nervous system causes an alteration of basic metabolic pathways. Furthermore, these alterations correlate with changes in the transcripts codifying for enzymes or proteins involved in these regulated pathways.
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