Metabolic fingerprints of proliferative diabetic retinopathy: an 1H-NMR-based metabonomic approach using vitreous humor.
OBJECTIVE
To explore the metabolic profile of vitreous fluid of 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 patients with type 1 diabetes with PDR and from 22 nondiabetic patients with macular hole (control group). Data analysis included a principal component analysis and partial least squares discriminant analysis (PLS-DA). In addition, 1H-(1)H and 1H-(13)C HMQC correlation spectra were acquired for the identification of metabolites. Furthermore, the main metabolites accounting for the differences in metabolic profile were assessed by current biochemical methods.


RESULTS
Lactate was the most abundant metabolite, and it was present at higher levels in samples from PDR patients than from nondiabetic patients (P=0.02). Glucose was significantly higher in samples from PDR patients than nondiabetic patients (P=0.03). After removing the lactate peak at 1.35 ppm and with the use of PLS-DA, a model was obtained that was able to correctly classify 19 of 22 patients with PDR and 18 of 22 controls, resulting in a sensitivity of 86% and a specificity of 81%. The main metabolites involved in this specific pattern recognition were galactitol and ascorbic acid (AA); levels of both were significantly lower in PDR patients.


CONCLUSIONS
1H-NMR-based metabonomic analysis of vitreous fluid permits the obtainment of a metabolic signature of PDR. Apart from the higher abundance of lactate and glucose, significant deficits of galactitol and AA are the main metabolic fingerprints of vitreous fluid from PDR patients.
Barba
Ignasi
I
Laboratory of Experimental Cardiology, Heart Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Garcia-Ramírez
Marta
M
Hernández
Cristina
C
Alonso
María Angeles
MA
Masmiquel
Lluis
L
García-Dorado
David
D
Simó
Rafael
R
D000328:Adult; D001205:Ascorbic Acid / Q000378:metabolism; D002247:Carbon Isotopes; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D004376:Galactitol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011522:Protons; D014822:Vitreous Body / Q000378:metabolism*
D002247:Carbon Isotopes; D011522:Protons; D004376:Galactitol; D019344:Lactic Acid; D005947:Glucose; D001205:Ascorbic Acid