Integration of vitreous metabolomics and lipidomics for vitreous-retina adhension in proliferative diabetic retinopathy

Abstract

Purpose : Retinal neovascularization (RNV) is the hallmark of ischemic retinopathy such as proliferative diabetic retinopathy (PDR) and the leading risk factor of permanent visual function loss. Abnormal vitreoretinal adhesion has been proved to lead the development of RNV in proliferative diabetic retinopathy (PDR). Endogenous metabolites and lipids underlying the abnormal vitreoretinal adhesion are of clinical interest but have not yet been well examined.

Methods : We collected the vitreous cavity fluid of 35 PDR patients with abnormal adhesion of epiretinal neovascular membrane and 30 age-matched fresh retinal detachment patients without Diabetes mellitus in Guangdong Principal People’s Hospital（GPPH). Metabolites and lipids were separated and acquired using ultra high-performance liquid chromatography (UHPLC) coupled to high-resolution Orbitrap mass spectrometry (MS). Multivariate statistical methods were performed to explore relations between two groups. All procedures comply with the principles set out in the Declaration of Helsinki and the Health Insurance Portability and Accountability Act.

Results : Differential expression analysis revealed significant vitreous metabolic and lipid differences between PDR patients exhibiting abnormal vitreoretinal adhesion and controls. A total of 165 metabolites and 37 lipids were identified with statistical significance (VIP>1, P<0.05).Pathway analysis showed that 21 pathway might be associated with the development of PDR, including cysteine and methionine metabolism; glycine, serine and threonine metabolism, etc. 11 lipid classes were found to be altered in PDR with abnormal vitreoretinal adhesion (P<0.05). Phosphatidylcholine, especially lysophosphatidylcholine was identified as a potential biomarker of the development of PDR. The correlation network revealed a significant interaction between altered lipids and other metabolites.

Conclusions : Based on vitreous metabolomic and lipidomic disorder of PDR may contribute to understand the pathogenesis of abnormal vitreoretinal adhesion and RNV formation in PDR and offer individualized treatment.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

 

Biomarkers evaluated via the absolute value of a Pearson correlation coefficient (PCC) >0.6.