Metabolomic analysis of human vitreous humor differentiates ocular inflammatory disease.
OBJECTIVE
Vitreoretinal disorders lack specific biomarkers that define either disease type or response to treatment. We have used NMR-based metabolomic analysis of human vitreous humor to assess the applicability of this approach to the study of ocular disease.


METHODS
Vitreous samples from patients with a range of vitreoretinal disorders were subjected to high-resolution (1)H-nuclear magnetic resonance spectroscopy (NMR). Good quality spectra were derived from the vitreous samples, and the profiles were analyzed by three different methods.


RESULTS
Principal component analysis (PCA) showed a wide dispersal of the different clinical conditions. Partial least squares discriminant analysis (PLS-DA) was used to define differences between lens-induced uveitis (LIU) and chronic uveitis (CU) and could distinguish between these conditions with a sensitivity of 78% and specificity of 85%. A genetic algorithm coupled with multivariate classification identified a small number of spectral components that showed clear discrimination between LIU and CU samples with sensitivity and specificity >90%. Assignment of specific resonances indicated that some metabolites involved in the arginase pathway were significantly more abundant in LIU than CU.


CONCLUSIONS
The discrimination we observed based on PCA, PLS-DA, and multivariate variable selection analysis of the NMR spectra suggests that a complex mix of metabolites are present in vitreous fluid of different uveitic conditions as a result of the disease process. Collectively the data demonstrates the efficacy of metabolomic analysis to distinguish between ocular inflammatory diseases.
Young
Stephen P
SP
Department of Rheumatology, University of Birmingham, Birmingham, UK.
Nessim
Maged
M
Falciani
Francesco
F
Trevino
Victor
V
Banerjee
Somnath P
SP
Scott
Robert A H
RA
Murray
Philip I
PI
Wallace
Graham R
GR
D015415:Biomarkers; D016000:Cluster Analysis; D003930:Diabetic Retinopathy / Q000378:metabolism; D005128:Eye Diseases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016018:Least-Squares Analysis; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D025341:Principal Component Analysis; D012680:Sensitivity and Specificity; D014605:Uveitis / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism; D014822:Vitreous Body / Q000737:chemistry / Q000378:metabolism*
D015415:Biomarkers