Langbøl Mia, Saruhanian Sarkis, Baskaran Thisayini, Tiedemann Daniel, Mouhammad Zaynab A, Toft-Kehler Anne Katrine, Jun Bokkyoo, Vohra Rupali, Bazan Nicolas G, Kolko Miriam
Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.
Neuroscience Center of Excellence, Louisiana State University Health New Orleans, New Orleans, LA 70112, USA.
J Clin Med. 2020 Sep 15;9(9):2979. doi: 10.3390/jcm9092979.
The main risk factor for primary open-angle glaucoma (POAG) is increased intraocular pressure (IOP). It is of interest that about half of the patients have an IOP within the normal range (normal-tension glaucoma, NTG). Additionally, there is a group of patients with a high IOP but no glaucomatous neurodegeneration (ocular hypertension, OHT). Therefore, risk factors other than IOP are involved in the pathogenesis of glaucoma. Since the retina has a very high oxygen-demand, decreased autoregulation and a fluctuating oxygen supply to the retina have been linked to glaucomatous neurodegeneration. To assess the significance of these mechanisms, we have utilized a human experimental model, in which we stress participants with a fluctuating oxygen supply. Levels of oxidative stress molecules, antioxidants, and lipid mediators were measured in the plasma. Patients with NTG, OHT, and control subjects were found to have similar levels of oxidative stress markers. In contrast, patients with OHT had a higher level of total antioxidant capacity (TAC) and pro-homeostatic lipid mediators. Thus, we suggest that OHT patients manage fluctuating oxygen levels more efficiently and, thus, are less susceptible to glaucomatous neurodegenerations, due to enhanced systemic antioxidant protection.
原发性开角型青光眼（POAG）的主要危险因素是眼压（IOP）升高。有趣的是，约一半的患者眼压在正常范围内（正常眼压性青光眼，NTG）。此外，还有一组眼压高但无青光眼性神经变性的患者（高眼压症，OHT）。因此，眼压以外的危险因素也参与了青光眼的发病机制。由于视网膜对氧气的需求量非常高，视网膜自身调节功能下降以及视网膜氧气供应波动与青光眼性神经变性有关。为了评估这些机制的重要性，我们利用了一种人体实验模型，在该模型中我们让参与者承受波动的氧气供应。测量了血浆中氧化应激分子、抗氧化剂和脂质介质的水平。发现NTG患者、OHT患者和对照组受试者的氧化应激标志物水平相似。相比之下，OHT患者的总抗氧化能力（TAC）和促稳态脂质介质水平较高。因此，我们认为OHT患者能更有效地应对波动的氧气水平，因此，由于全身抗氧化保护增强，他们对青光眼性神经变性的易感性较低。
