Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, Building 22, 2100, Copenhagen Ø, Denmark.
Department of Veterinary & Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Cell Mol Neurobiol. 2024 Aug 16;44(1):59. doi: 10.1007/s10571-024-01492-3.
Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before ("baseline"), during ("hypoxia"), and after hypoxia ("recovery"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP.
原发性开角型青光眼（POAG）根据眼压进行细分。正常眼压青光眼（NTG）患者的眼压从未测量过高，而高眼压症（OHT）患者的眼压高，但没有青光眼的迹象。虽然眼压被认为是所有青光眼患者的一个危险因素，但可以合理假设其他危险因素，如炎症，也发挥作用。我们旨在描述 NTG（n = 10）、OHT（n = 10）和对照组（n = 10）患者血浆在缺氧期间的蛋白质组和细胞因子谱。参与者暴露于缺氧 2 小时，随后进行 30 分钟的常氧。在“基线”（缺氧前）、“缺氧”（缺氧期间）和“恢复”（缺氧后）时取样。基于液相色谱与质谱联用（LC-MS）的蛋白质组学进行分析。通过 Luminex 测定法测量细胞因子。生物信息学分析表明补体和凝血级联在 NTG 和 OHT 中涉及。高密度脂蛋白 3（HDL3）载脂蛋白的调节表明胆固醇代谢的变化与 OHT 有关。与对照组相比，OHT 患者的肿瘤坏死因子-α（TNF-α）水平在缺氧时降低。与对照组相比，NTG 患者在缺氧期间循环白细胞介素-1β（IL-1β）和 C 反应蛋白（CRP）水平降低。恢复后，NTG 和 OHT 患者的血浆白细胞介素-6（IL-6）上调。目前的结果表明，NTG 和 OHT 患者的全身免疫反应增强，这与青光眼的发病事件相关。载脂蛋白可能具有抗炎作用，使 OHT 患者能够耐受炎症和青光眼的发展，尽管眼压高。
