Choi Jin A, Ju Hyun-Hee, Lee Jiyoung, Kim Ju-Eun, Paik Soon-Young, Skiba Nikolai P, Rao Ponugoti Vasantha
Department of Ophthalmology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon 16247, Korea.
Department of Ophthalmology, College of Medicine, Daejon St. Mary's Hospital, The Catholic University of Korea, Daejon 34943, Korea.
J Clin Med. 2022 Apr 22;11(9):2337. doi: 10.3390/jcm11092337.
Herpetic anterior uveitis-associated ocular inflammation is commonly manifested with ocular hypertension and glaucoma. Relative to other viruses, cytomegalovirus (CMV) positive hypertensive anterior uveitis is associated with high recurrences of uveitis, as well as with uncontrolled intraocular pressure (IOP) and a subsequent higher requirement for future glaucoma surgery. To gain novel insights into the pathogenesis of ocular hypertension in these patients, we investigated the proteome changes of the aqueous humor (AH) derived from the CMV hypertensive anterior uveitis (CMV-HAU; = 10) patients and non-glaucoma (cataract; = 10) patients using liquid chromatography with tandem mass spectrometry. Among a total of 562 proteins identified, fifty and fifteen proteins were significantly elevated and decreased, respectively, in the AH of CMV-HAU patients compared to the control subjects by ≥2 fold. Gene ontology (GO) enrichment and network analyses of elevated proteins revealed that the enrichment of protein was involved in the complement activation, the humoral immune response mediated by the circulating immunoglobulins, proteolysis, and platelet degranulation. In the AH of CMV-HAU, GDF (growth/differentiation factor)-15, the inflammatory marker belonging to the TGF-β superfamily proteins, was significantly increased, while vasorin, an anti-TGF-β protein, levels were decreased. The trabecular meshwork cells infected with CMV exhibited a significantly increased expression of inflammatory markers. Collectively, these data indicate increased complement factor associated inflammation and humoral immunity in CMV-HAU associated ocular hypertension.
疱疹性前葡萄膜炎相关的眼部炎症通常表现为眼压升高和青光眼。相对于其他病毒，巨细胞病毒（CMV）阳性的高血压性前葡萄膜炎与葡萄膜炎的高复发率相关，也与眼压（IOP）控制不佳以及随后对未来青光眼手术的更高需求相关。为了深入了解这些患者眼压升高的发病机制，我们使用液相色谱串联质谱法研究了来自CMV高血压性前葡萄膜炎（CMV-HAU；n = 10）患者和非青光眼（白内障；n = 10）患者的房水（AH）的蛋白质组变化。在总共鉴定出的562种蛋白质中，与对照受试者相比，CMV-HAU患者的AH中分别有50种和15种蛋白质显著升高和降低≥2倍。对升高蛋白质的基因本体（GO）富集和网络分析表明，蛋白质的富集涉及补体激活、循环免疫球蛋白介导的体液免疫反应、蛋白水解和血小板脱颗粒。在CMV-HAU的AH中，属于TGF-β超家族蛋白的炎症标志物生长/分化因子（GDF）-15显著增加，而抗TGF-β蛋白血管调节蛋白的水平降低。感染CMV的小梁网细胞表现出炎症标志物的表达显著增加。总体而言，这些数据表明在CMV-HAU相关的眼压升高中补体因子相关炎症和体液免疫增加。
