JAMA ophthalmology · 2014
Thin central corneal thickness and early-onset glaucoma in lacrimo-auriculo-dento-digital syndrome.
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Ghini Veronica, Cosottini Lucrezia, Scordino Miriana, Ricciardi Nicolò, Urone Giulia, Gambino Giuditta, Di Liberto Valentina, Turano Paola
Аннотация
INTRODUCTION: Temporal lobe epilepsy is associated with systemic metabolic alterations that may evolve during disease progression and in response to pharmacological treatment. This study employed a longitudinal 1H NMR-based metabolomics approach to characterize the serum metabolic profile of a chronic pilocarpine-induced rat model of temporal lobe epilepsy.
METHODS: Serum samples were collected longitudinally to identify phase-specific metabolic signatures. Following phenobarbital administration, animals were classified as drug-sensitive or drug-resistant according to their treatment response. The resulting metabolic profiles were investigated using multivariate and univariate statistical analyses.
RESULTS: The analysis revealed progressive systemic metabolic remodeling characterized by extensive alterations in lipid-related signals and significant increases in the ketone bodies 3-hydroxybutyrate and acetoacetate, as well as in glutamine. Following phenobarbital treatment, OPLS-DA showed a strong metabolic similarity between the drug-sensitive and drug-resistant groups, which occupied nearly identical metabolic spaces. Nevertheless, after stratification, creatine emerged as the only significantly different metabolite between responders and non-responders (p = 0.001).
DISCUSSION: The convergence of the metabolic profiles of drug-sensitive and drug-resistant animals suggests that the systemic effects of chronic epilepsy and phenobarbital treatment dominate the serum metabolome, potentially masking subtle molecular signatures associated with drug resistance. Creatine represents a notable exception and warrants further investigation as a potential marker distinguishing responders from non-responders.
METHODS: Serum samples were collected longitudinally to identify phase-specific metabolic signatures. Following phenobarbital administration, animals were classified as drug-sensitive or drug-resistant according to their treatment response. The resulting metabolic profiles were investigated using multivariate and univariate statistical analyses.
RESULTS: The analysis revealed progressive systemic metabolic remodeling characterized by extensive alterations in lipid-related signals and significant increases in the ketone bodies 3-hydroxybutyrate and acetoacetate, as well as in glutamine. Following phenobarbital treatment, OPLS-DA showed a strong metabolic similarity between the drug-sensitive and drug-resistant groups, which occupied nearly identical metabolic spaces. Nevertheless, after stratification, creatine emerged as the only significantly different metabolite between responders and non-responders (p = 0.001).
DISCUSSION: The convergence of the metabolic profiles of drug-sensitive and drug-resistant animals suggests that the systemic effects of chronic epilepsy and phenobarbital treatment dominate the serum metabolome, potentially masking subtle molecular signatures associated with drug resistance. Creatine represents a notable exception and warrants further investigation as a potential marker distinguishing responders from non-responders.