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[原发性开角型青光眼神经视网膜保护的分子机制]

[Molecular mechanisms of neuroretinoprotection in primary open-angle glaucoma].

作者信息

Gabdrakhmanova A F, Aznabaeva L F, Abizgil'dina G Sh, Kurbanov S A

机构信息

Bashkir State Medical University, 3 Lenina St., Ufa, Republic of Bashkortostan, Russian Federation, 450008.

Medical center 'DuplexMed', 103A Artema St., Sterlitamak, Russian Federation, 453100.

出版信息

Vestn Oftalmol. 2018;134(5):54-60. doi: 10.17116/oftalma201813405154.

DOI:10.17116/oftalma201813405154
PMID:30499540
Abstract

PURPOSE

To evaluate the effectiveness of neuroprotective therapy in patients with primary open-angle glaucoma based on specific biochemical markers of neurotrophy and neurodegeneration.

MATERIAL AND METHODS

In the course of the study, lacrimal fluid (LF) of 23 patients (46 eyes) with stage I-II primary open angle glaucoma (POAG) aged 66.3±10.8 was examined. The control group consisted of healthy individuals (12 control LF samples). Local antihypertensive therapy was complimented with 10 intramuscular injections of retinalamin (GEROPHARM LLC, St. Petersburg) - a complex of peptides isolated from cattle retinas, administered 5 mg once a day. Enzyme immunoassay (ELISA) method was used to test LF for concentrations of brain-derived neurotrophic factor (BDNF) and neuron specific enolase (NSE) before and after the treatment.

RESULTS

In healthy subjects, the content of BDNF was 0.83±0.06 ng/mL, NSE - 0.51±0.06 ng/mL. In patients with POAG, the indices were higher: BDNF was 1.39±0.85 ng/mL (p>0.05), NSE - 4.31±2.02 ng/mL (p<0.05). The patients with stage II-III POAG had a significant increase of BDNF concentration (1.37±0.41 ng/mL and 1.52±0.40 ng/mL respectively in stages II and III) indicating compensatory capabilities at these stages of the disease. The NSE marker was also high in these stages (4.16±2.44 ng/mL and 5.78±2.80 ng/mL, p<0.05), which indicates the degeneration of retinal ganglion cells. After Retinalamin® therapy, patients with stage II POAG had control group levels of marker proteins, while in stage III patients NSE content remained high.

CONCLUSION

There is a compensatory increase of BDNF level and a pathological increase of NSE content in LF of POAG patients. The change in the content of neurotrophins in the LF was determined to depend on the stage of POAG. Thus, in stages II and III POAG there is a marked increase of NSE and a compensatory increase of BDNF. After the complex therapy including retinalamin in patients with stage II POAG, a decrease in initially high concentrations of BDNF and NSE in LF down to the control group values was noted. In stage III patients, signs of neurodegeneration persist in the form of high NSE values. Taking into account the positive dynamics of the neuronal marker content in LF in the complex therapy of POAG with Retinalamin®, timely neuroretinoprotection is recommended.

摘要

目的

基于神经营养和神经退行性变的特定生化标志物,评估神经保护疗法对原发性开角型青光眼患者的有效性。

材料与方法

在研究过程中,对23例年龄为66.3±10.8岁的I-II期原发性开角型青光眼(POAG)患者(46只眼)的泪液(LF)进行了检测。对照组由健康个体组成(12份对照LF样本)。局部抗高血压治疗辅以10次视网膜胺(GEROPHARM LLC,圣彼得堡)肌肉注射,视网膜胺是从牛视网膜中分离出的一种肽复合物,每天注射1次,每次5mg。采用酶联免疫吸附测定(ELISA)法检测治疗前后LF中脑源性神经营养因子(BDNF)和神经元特异性烯醇化酶(NSE)的浓度。

结果

在健康受试者中,BDNF含量为0.83±0.06 ng/mL,NSE为0.51±0.06 ng/mL。在POAG患者中,这些指标较高:BDNF为1.39±0.85 ng/mL(p>0.05),NSE为4.31±2.02 ng/mL(p<0.05)。II-III期POAG患者的BDNF浓度显著升高(II期和III期分别为1.37±0.41 ng/mL和1.52±0.40 ng/mL),表明在疾病的这些阶段具有代偿能力。这些阶段的NSE标志物也较高(4.16±2.44 ng/mL和5.78±2.80 ng/mL,p<0.05),这表明视网膜神经节细胞发生了退变。视网膜胺治疗后,II期POAG患者的标志物蛋白水平达到对照组水平,而III期患者的NSE含量仍然较高。

结论

POAG患者LF中BDNF水平有代偿性升高,NSE含量有病理性升高。LF中神经营养因子含量的变化取决于POAG的阶段。因此,在II期和III期POAG中,NSE显著升高,BDNF有代偿性升高。在II期POAG患者中进行包括视网膜胺在内的综合治疗后,LF中最初较高浓度的BDNF和NSE降低至对照组水平。在III期患者中,神经退行性变的迹象以高NSE值的形式持续存在。考虑到在POAG与视网膜胺的综合治疗中LF中神经元标志物含量的积极变化,建议及时进行神经视网膜保护。

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