Siegfried Carla J, Shui Ying-Bo, Tian Baohe, Nork T Michael, Heatley Gregg A, Kaufman Paul L
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States.
Department of Ophthalmology & Visual Sciences, School of Medicine & Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States.
Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4003-4014. doi: 10.1167/iovs.17-21890.
The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, aqueous humor antioxidant-oxidant balance, aqueous humor dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey.
Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous humor specimens were analyzed for antioxidant status and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis.
pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the aqueous humor only in the surgical eyes.
Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.
本研究旨在评估玻璃体切除术(PPV)联合晶状体摘除及人工晶状体植入术(PE/IOL)对老年猕猴分子氧(pO2)分布、房水抗氧化-氧化平衡、房水动力学以及小梁网(TM)组织病理学变化的影响。
对6只恒河猴进行PPV,随后进行PE/IOL。测量pO2、房水流出易度和眼压(IOP)。分析房水和玻璃体标本的抗氧化状态以及氧化损伤标志物8-羟基-2'-脱氧鸟苷(8-OHdG)。获取TM标本进行免疫组织化学和定量PCR分析。
基线时pO2在前房显示出陡峭的梯度,在后房(PC)和晶状体周围水平较低。PPV和PE/IOL后,PC、人工晶状体周围和房角的pO2显著增加。两种手术干预后IOP均升高,房水流出易度无变化。组织病理学分析未显示TM细胞定量变化,但8-OHdG增加。定量PCR未揭示青光眼相关基因表达的显著差异。房水和玻璃体分析显示,仅手术眼的房水中抗坏血酸和总活性抗氧化潜能降低,8-OHdG增加。
老年恒河猴的氧分布在基线和手术干预后与人类相似。我们关于TM氧化损伤的组织病理学变化以及氧化-抗氧化平衡改变的研究结果表明,增加的氧暴露与氧化应激/损伤以及开角型青光眼的发生之间可能存在相关性。