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.

Conclusion: 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.

目的：增殖性糖尿病视网膜病变（PDR）引起的大面积视网膜缺血可发展为新生血管性青光眼（NVG）。我们通过分析继发于 PDR 的 NVG 患者的房水 (AH) 蛋白质组学来寻找可能参与新血管形成的蛋白质，以增加对新血管形成可能机制的理解。

方法：我们收集了PDR继发NVG患者的12个AH样本（A组）作为实验组，收集了没有糖尿病视网膜病变的原发性急性闭角型青光眼（PAACG）和糖尿病患者的7个AH样本（B组）。 (NDR) 作为对照组。基于数据独立采集 (DIA) 方法对房水样品进行差异定量蛋白质组分析。差异表达的蛋白质通过 Ingenuity Pathway Analysis (IPA) 进行功能注释。通过平行反应监测（PRM）方法在另一组（A组：5个样品和B组：5个样品）中验证了重要的差异表达蛋白。

结果：共鉴定出636个AH蛋白，82个蛋白在两组间差异表达。功能注释表明差异表达的蛋白质主要与血管生成和细胞迁移有关。信号通路分析表明，A组蛋白上调主要与肝X受体/维甲酸X受体（LXR/RXR）激活和急性反应有关。

结论：本研究提出了一项与继发于 PDR 的 NVG 相关的试点工作，它提供了对 NVG 病理生理学控制机制的更好理解。