Proteomics of Vitreous Humor Reveals PPARA, RXR, and LXR Are Possible Upstream Regulators of Proliferative Diabetic Retinopathy

Purpose: To investigate the key regulators of the disease by comparing the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and the controls with idiopathic epiretinal membrane (iERM). Methods: Vitreous humor (VH) samples were derived from patients with PDR or iERM through the pars plana vitrectomy. The VH proteins were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. MaxQuant software and Metascape were applied to explore the enrichment of differentially expressed proteins in biological processes, cellular components, and molecular functions. Enrichr online tool and Gene Set Enrichment Analysis (GSEA) were performed to detect upstream transcriptional regulators of the highly expressed proteins. Results: The present study collected 8 vitreous humor samples from 5 PDR eyes and 3 iERM eyes and identified 88 highly expressed proteins in PDR patients. We validated our highly expressed proteome was able to distinguish the PDR patients from the non-PDR patients by using the VH proteomics data from a previous study. The majority of highly expressed proteins were involved in complement and coagulation cascades, regulating exocytosis, and hemostasis. Using the Gene Set Enrichment Analysis (GSEA), we identified that transcription factors (TFs) PPAR-α, RXR, LXR regulate these proteins. Conclusions: In this study, we identified a highly expressed proteome in VH of PDR patients. The role of the complement and coagulation system, regulating exocytosis, and hemostasis has been of great significance to PDR. Nuclear receptors PPARA, RXR, LXR were possible upstream regulators of disease progression and required further study.