Proteomic Analysis of Aqueous Humor Proteins Associated with Neovascular Glaucoma Secondary to Proliferative Diabetic Retinopathy

Abstract

Objective: Extensive retinal ischemia caused by proliferative diabetic retinopathy (PDR) may develop into neovascular glaucoma (NVG). We searched for the proteins which might participate in neovascularization through the analysis of aqueous humor (AH) proteomics in patients with NVG secondary to PDR to increasing the understanding of the possible mechanism of neovascularization. Methods: We collected 12 samples (group A) of AH from patients with NVG secondary to PDR as the experimental group and 7 samples (group B) of AH from patients with primary acute angle-closure glaucoma (PAACG) & diabetes mellitus without diabetic retinopathy (NDR) as the control group. Differential quantitative proteome analysis of the aqueous humor samples was performed based on the data-independent acquisition (DIA) method. The differentially expressed proteins were functionally annotated by Ingenuity Pathway Analysis (IPA). The important differentially expressed proteins were validated in another group (group A: 5 samples and group B: 5 samples) by parallel reaction monitor (PRM) approach. Results: A total of 636 AH proteins were identified, and 82 proteins were differentially expressed between the two groups. Functional annotation showed that the differentially expressed proteins were mainly associated with angiogenesis and cell migration. Signaling pathways analysis showed that the proteins up-regulated in group A were mainly related to Liver X receptor/Retinoid X receptor (LXR/RXR) activation and acute reaction. Conclusions: This study presented a pilot work related to NVG secondary to PDR, which provided a better understanding of the mechanisms governing the pathophysiology of NVG.