Vitreous metabolomics profiling of proliferative diabetic retinopathy

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Vitreous metabolomics profiling of proliferative diabetic retinopathy Yohei Tomita 1,2 & Gael Cagnone 3 & Zhongjie Fu 1,4 & Bertan Cakir 1 & Yumi Kotoda 1 & Masaki Asakage 5 & Yoshihiro Wakabayashi 5 & Ann Hellström 6 & Jean-Sébastien Joyal 3,7 & Saswata Talukdar 8 & Lois E. H. Smith 1 Yoshihiko Usui 5

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Received: 2 July 2020 / Accepted: 10 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Aims/hypothesis Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. Methods We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27–80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. Results We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate