Year: 2015
Type: article
Study design: Observational Study
Abstract: Proliferative diabetic retinopathy (PDR) is the most severe form of diabetic retinopathy and, along with diabetic macular edema, is responsible for the majority of blindness in adults below the age of 65. Therapeutic strategies for PDR are ineffective at curtailing disease progression in all cases; however a deeper understanding of the ocular metabolic landscape in PDR through metabolomic analysis may offer new therapeutic targets. Here, global and targeted mass spectrometry-based metabolomics were used to investigate metabolism. Initial analyses on vitreous humor from patients with PDR (n = 9) and non-diabetic controls (n = 11) revealed an increase of arginine and acylcarnitine metabolism in PDR. The oxygen-induced-retinopathy (OIR) mouse model, which exhibits comparable pathological manifestations to human PDR, revealed similar increases of arginine and other metabolites in the urea cycle, as well as downregulation of purine metabolism. We validated our findings by targeted multiple reaction monitoring and through the analysis of a second set of patient samples [PDR (n = 11) and non-diabetic controls (n = 20)]. These results confirmed a predominant and consistent increase in proline in both the OIR mouse model and vitreous samples from patients with PDR, suggesting that over activity in the arginine-to-proline pathway could be used as a therapeutic target in diabetic retinopathy.
Source: Metabolomics
Authors: Liliana P. Paris, Caroline H. Johnson, Edith Aguilar, Yoshihiko Usui, Kevin Cho, Lihn T. Hoang, Daniel Feitelberg, H. Paul Benton, Peter D. Westenskow, Toshihide Kurihara, Jennifer Trombley, Kinya Tsubota, Shunichiro Ueda, Yoshihiro Wakabayashi, Gary J. Patti, Julijana Ivanisevic, Gary Siuzdak, Martin Friedlander
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,890
Funders: California Institute of Regenerative Medicine, Lowy Medical Research Institute, Calouste Gulbenkian Foundation, Manpei Suzuki Diabetes Foundation, Fundação Champalimaud, National Institutes of Health, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Eye Institute, National Cancer Institute, Alcon Japan
Awards: G1307824525, Approach for retinal diseases based on regulation of hypoxia response, Normalizing Breast Cancer Metabolism to Prevent Progression and Recurrence (PQ21), Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center, Griffin: Venous Thromboembolism and mass spectrometry-based untargeted metabolomi, Adult Stem Cells for Therapy of Visual Disorders, Proteomic Strategies for AIDS and Drug Abuse - HIV and METH CNS Synergy, MicroRNAs for therapy of visual disorders, G71690937, Integrins and Ocular Angiogenesis, G9000346257
OpenAlex ID: W2175441873