Abstract
To determine the plasma metabolomic profile of exudative age-related macular degeneration (AMD), we performed a targeted metabolomics study on the plasma from patients (n = 40, mean age = 81.1) compared to an age- and sex-matched control group (n = 40, mean age = 81.8). All included patients had documented exudative AMD, causing significant visual loss (mean logMAR visual acuity = 0.63), compared to the control group. Patients and controls did not differ in terms of body mass index and co-morbidities. Among the 188 metabolites analyzed, 150 (79.8%) were accurately measured. The concentrations of 18 metabolites were significantly modified in the AMD group, but only six of them remained significantly different after Benjamini–Hochberg correction. Valine, lysine, carnitine, valerylcarnitine and proline were increased, while carnosine, a dipeptide disclosing anti-oxidant and anti-glycating properties, was, on average, reduced by 50% in AMD compared to controls. Moreover, carnosine was undetectable for 49% of AMD patients compared to 18% in the control group (p-value = 0.0035). Carnitine is involved in the transfer of fatty acids within the mitochondria; proline, lysine and valerylcarnitine are substrates for mitochondrial electrons transferring flavoproteins, and proline is one of the main metabolites supplying energy to the retina. Overall, our results reveal six new metabolites involved in the plasma metabolomic profile of exudative AMD, suggesting mitochondrial energetic impairments and carnosine deficiency.
Highlights
Age-related macular degeneration (AMD) is one of the leading causes of visual impairment in the elderly [1], affecting 30–50 million individuals worldwide [2]
The visual prognosis of exudative AMD has been significantly improved by intravitreal injection of anti-vascular endothelial growth factor agents [3], but the metabolic disturbances contributing to the dysfunction of the retinal pigment epithelium (RPE) and, secondarily, the loss of photoreceptors, remain poorly understood [4,5]
An untargeted metabolomics study performed on the plasma of exudative AMD patients (n = 20), compared to healthy controls (n = 20), identified 10 discriminating metabolites, including amino acids, palmitoylcarnitine, isomaltose, hydrocortisone and biliverdin [8]
Summary
Age-related macular degeneration (AMD) is one of the leading causes of visual impairment in the elderly [1], affecting 30–50 million individuals worldwide [2]. The visual prognosis of exudative AMD has been significantly improved by intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents [3], but the metabolic disturbances contributing to the dysfunction of the retinal pigment epithelium (RPE) and, secondarily, the loss of photoreceptors, remain poorly understood [4,5]. The few metabolic studies previously performed in AMD patients were recently reviewed [6]. A first study was performed using untargeted mass spectrometry in the plasma of neovascular AMD patients (n = 26) compared to controls (n = 19). An untargeted metabolomics study performed on the plasma of exudative AMD patients (n = 20), compared to healthy controls (n = 20), identified 10 discriminating metabolites, including amino acids, palmitoylcarnitine, isomaltose, hydrocortisone and biliverdin [8]
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