Papadopoulou Garyfallia, Zisimopoulos Dimitrios, Kalaitzopoulou Electra, Makri Olga Ε, Tsapardoni Foteini N, Georgakopoulos Constantinos D, Georgiou Christos D
Department of Biology, University of Patras, Patras, Greece.
Department of Ophthalmology, University of Patras, Patras, Greece.
Mol Vis. 2018 Dec 31;24:890-901. eCollection 2018.
The aim of this study is to investigate the age-correlation of oxidative stress (OS, assessed by the accumulative OS damage marker protein carbonyls) in aqueous humour (AH; together with protein concentration) and lens epithelial cells plus capsule (LECs/capsule) in patients with cataract (CAT), and also suffering from pseudoexfoliation syndrome (PEX), primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG).
AH samples from 78 male/female patients (21, 20, 19 and 18 with CAT, PEX, PXG, and POAG, respectively), and LECs/capsule samples from 104 male/female patients (34, 32, 18, and 20 with CAT, PEX, PXG and POAG, respectively) were collected during phacoemulsification CAT surgery. Average protein carbonyl concentrations were measured in patients grouped in 5-year age intervals (ranging from 56-60 to 86-90). The non-overlapping age ranges and numbers of the tested subjects did not allow comparative follow up studies for the tested diseases.
There is an age-dependent increase of protein carbonyls in AH (nmol mg protein and ml), and in the order CAT<PXG=POAG<PEX and CAT<PEX=POAG<PXG respectively. Moreover, protein concentration in AH accumulates in the order CAT<PEX<POAG<PXG but is not age-related. An age-dependent increase of protein carbonyls (nmol mg protein) is also observed in LECs/capsule, and in the order CAT<PEX=~POAG<PXG.
The present study shows for the first time an age-increased OS-induced protein damage (protein carbonyl formation) in the AH and LECs/capsule of CAT patients with PEX, POAG or PXG. The slow rate of change of protein carbonyls strongly suggests a long-term implication of OS in ocular disease pathogenesis. Additionally, protein concentration levels in the AH of CAT patients increase independently of age, and in same as with protein carbonyls increasing order levels for CAT<POAG<PXG in AH and LECs/capsule. This may suggest a protein cross-diffusion taking place between AH and LECs/capsule, most likely originating from PEX deposition and/or necrotic/apoptotic LECs/capsule. Moreover, the findings of the present study establish the use of protein carbonyls (together with a methodology for their more accurate quantification, which overcomes serious unreliability problems of past methods) as an age accumulative marker of OS damage, for future studies that investigate long-term OS involvement in pseudoexfoliative ocular disorders.
本研究旨在调查白内障（CAT）患者，同时患有假性剥脱综合征（PEX）、原发性开角型青光眼（POAG）和假性剥脱性青光眼（PXG）的房水（AH；连同蛋白质浓度）以及晶状体上皮细胞加囊膜（LECs/囊膜）中氧化应激（OS，通过累积的OS损伤标志物蛋白质羰基评估）与年龄的相关性。
在白内障超声乳化手术期间，收集了78例男性/女性患者的AH样本（分别有21例、20例、19例和18例患有CAT、PEX、PXG和POAG），以及104例男性/女性患者的LECs/囊膜样本（分别有34例、32例、18例和20例患有CAT、PEX、PXG和POAG）。将患者按5年年龄间隔分组（范围从56 - 60岁到86 - 90岁）测量平均蛋白质羰基浓度。测试对象的非重叠年龄范围和数量不允许对所测试疾病进行比较性随访研究。
AH中蛋白质羰基（nmol/mg蛋白质和/ml）呈年龄依赖性增加，顺序分别为CAT<PXG=POAG<PEX以及CAT<PEX=POAG<PXG。此外，AH中的蛋白质浓度按CAT<PEX<POAG<PXG的顺序累积，但与年龄无关。在LECs/囊膜中也观察到蛋白质羰基（nmol/mg蛋白质）呈年龄依赖性增加，顺序为CAT<PEX=~POAG<PXG。
本研究首次表明，患有PEX、POAG或PXG的白内障患者的AH和LECs/囊膜中，OS诱导的蛋白质损伤（蛋白质羰基形成）随年龄增加。蛋白质羰基的缓慢变化速率强烈表明OS在眼部疾病发病机制中具有长期影响。此外，白内障患者AH中的蛋白质浓度水平随年龄独立增加，且与AH和LECs/囊膜中蛋白质羰基增加顺序相同，即CAT<POAG<PXG。这可能表明在AH和LECs/囊膜之间发生了蛋白质交叉扩散，最有可能源自PEX沉积和/或坏死/凋亡的LECs/囊膜。此外，本研究结果确立了将蛋白质羰基（连同其更准确量化的方法，该方法克服了过去方法严重的不可靠问题）用作OS损伤的年龄累积标志物，用于未来研究长期OS在假性剥脱性眼部疾病中的作用。
