Metabolic fingerprints of proliferative diabetic retinopathy. An 1H NMR-based metabonomic approach using vitreous humor -- Barba et al., 10.1167/iovs.10-5348 -- Investigative Ophthalmology & Visual Science

P/P, published online ahead of print April 7, 2010
(Investigative Ophthalmology and Visual Science. )
© 2010 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.10-5348

Metabolic fingerprints of proliferative diabetic retinopathy. An 1H NMR-based metabonomic approach using vitreous humor
Ignasi Barba,1 Marta Garcia-Ramirez,2 Cristina Hernandez,3 Maria A Alonso,4 Lluis Masmiquel,5 David Garcia-Dorado,6 and Rafael Simó7

1Laboratory of Experimental Cardiology, Heart Department, Instituto de Salud Carlos III, Barcelona, Spain 2Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain 3Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain 4Barcelona, Spain 5Barcelona, Spain 6Barcelona, Spain 7Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain


Correspondence: Rafael Simó, Email: rsimo@ir.vhebron.net

Abstract

PURPOSE: To explore the metabolic profile of vitreous fluid from patients with proliferative diabetic retinopathy (PDR) using 1H NMR based metabonomic analysis.

METHODS: 1H NMR spectra were acquired from vitreous samples obtained during vitrectomy from 22 type 1 diabetic patients with PDR and 22 from non-diabetic patients with macular hole (control group). Data analysis included a principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). In addition, 1H-1H and 1H-13C HMQC correlation spectra were acquired for the identification of metabolites. Furthermore, the main metabolites accounting for the differences in metabolic profile were also assessed by current biochemical methods.

RESULTS: Lactate was the most abundant metabolite and it was higher in samples from PDR patients than non-diabetic patients (p=0.02). Glucose was significantly higher in samples from PDR patients than non-diabetic patients (p=0.03). After removing the lactate peak at 1.35 ppm, and using PLS-DA, a model was obtained which was able to correctly classify 19 out of 22 patients with PDR and 18 out of 22 controls, resulting in a sensitivity of 86% and a specificity of 81%. The main metabolites involved in this specific pattern recognition were galactitiol and ascorbic acid (AA), and they were significantly lower in PDR patients.

CONCLUSIONS: 1H NMR based metabonomic analysis of vitreous fluid permits to obtain a metabolic signature of PDR. Apart from the higher abundance of lactate and glucose, significant deficits of galactitiol and AA are the main metabolic fingerprints of vitreous fluid from PDR patients.


Key Words: diabetic retinopathy • vitreous humor • metabonomics

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Metabolic fingerprints of proliferative diabetic retinopathy. An 1H NMR-based metabonomic approach using vitreous humor -- Barba et al., 10.1167/iovs.10-5348 -- Investigative Ophthalmology & Visual Science