A Plasma Metabolomic Profiling of Exudative Age-Related Macular Degeneration Showing Carnosine and Mitochondrial Deficiencies

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.

Metabolomics in Age-Related Macular Degeneration: A Systematic Review

“…Three of the studies were by the same author on the same cohort, but there were differences in sample size, biological samples, test platform, and research grouping, so all of them were included in this review. 25 – 27 A total of four types of sampled tissues were involved in the study, including serum (n = 3), 4 , 10 , 28 plasma (n = 7), 25 , 27 , 29 – 33 urine (n = 1), 26 aqueous humor (n = 1), and both serum and plasma (n = 1). 34 , 35 With regard to the analytical platforms used for metabolite detection, 10 studies used MS, and the other three used the NMR platform.…”

“…Among the 13 studies, two did not explicitly describe the inclusion criteria of the subjects, 29 , 31 and four did not consider the overfitting of the analysis model. 4 , 30 , 33 , 34 …”

“…Osborn et al 31 found that a panel of metabolites differed between NVAMD patients and controls, such as tyrosine metabolism, sulfur amino acid metabolism and amino acid. Chao de la Barca et al 33 revealed six new metabolites involved in the plasma metabolomic profile, suggesting mitochondrial energetic impairments and carnosine deficiency might play a role in NVAMD. Han et al 35 used aqueous humor samples and obtained 18 metabolites with significant differences.…”

Proline metabolism and transport in retinal health and disease

“…Multiple metabolomics studies identified significant changes in proline in AMD patients (Hou et al 2020) (Table 2). A recent targeted-metabolomics study also found proline to be one of six significantly changed metabolites among the 188 metabolites analyzed in the plasma of AMD patients (Chao de la Barca et al 2020).…”

COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?

“…Importantly, these levels decline in elderly humans [ 38 ] and low levels of acetyl-carnosine are associated with enhanced frailty [ 39 ]. Low carnosine levels have also been detected in blood from patients suffering from age-related macular degeneration [ 40 ].…”