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Jianhai Du, Haiwei Gu, Sally J Turner, Danijel Djukovic, Daniel Raftery, James B Hurley; Metabolite profiles of rod photoreceptor cell death in mouse retinal degeneration models. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4374.
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© ARVO (1962-2015); The Authors (2016-present)
To identify metabolites and metabolic pathways related to rod photoreceptor cell death.
Retinas from retinal degeneration 1 (rd1), retinal degeneration 10 (rd10), Aryl Hydrocarbon Receptor-Interacting Protein-Like (AIPL1-/-) and age-matched wild-type (WT) mice were collected from postnatal day 8 to 20. The metabolites from the retinas were extracted and analyzed by LC-MS for targeted metabolomics. The data were normalized, statistically analyzed and enriched for metabolic pathways using MetaboAnalyst 2.0.
We detected 129-133 metabolites in total in the retina samples. In all the three models, we identified metabolites that were significantly changed before, at the onset and at the early stage of retinal degeneration. Metabolites with altered levels are involved in the metabolism of purine, pyrimidine, amino acids, phospholipid, glycerolipids, glycolysis, TCA cycle and protein biosynthesis. One of the striking common features in all these models is the stimulation of metabolites in the purine metabolism pathway such as xanthine and hypoxanthine. The long-lasting inhibition of cGMP breakdown may disrupt purine metabolism, resulting in cell damage. At all time-points, glycerate was increased about 10-20 fold in AIPL1-/- mice, and acetylcholine was increased but oxaloacetate was decreased in Rd10 mice. The different metabolite profiles for these models indicate that there may be differences in the mechanism of cell death in each of these models.
Metabolic profile changes prior to rod photoreceptor cell death and the involvement of purine metabolism may provide potential therapeutic targets to slow or prevent retinal degeneration.
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