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首页> 外文期刊>Molecular medicine reports >Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats
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Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

机译：玻璃体腔注射Y-27632 Rho相关蛋白激酶抑制剂对皇家外科学院大鼠的光感受器保护

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摘要

Retinitis pigmentosa (RP) is an inherited retinal disease, which is characteristic by degeneration of the rod and cone photoreceptors. The present study aimed to assess the protective effects on photoreceptors of intravitreal injection of Y-27632, a specific inhibitor of Rho-associated protein kinase (ROCK), in a Royal College of Surgeons (RCS) rat model. Different concentrations of Y-27632 (1-50 mM) were administered by intravitreal injection into the RCS rats. The effects of Y-27632 were recorded using electroretinography (ERG), measuring the thicknesses of the retinal outer nuclear layer (ONL) and examination of apoptotic markers using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and western blot analysis. Treatment of the eyes with Y27632 at 10 or 50 mM, led to a 30% increase in a-and b-wave amplitudes in ERG, and an increase in ONL thickness by 10%, compared with the 1 mM Y-27632-treated and vehicle (phosphate-buffered saline; PBS)-treated groups. In addition, eyes treated with 10 mM Y27632 exhibited a 90% decrease in TUNEL-positive cells, accompanied by decreased protein expression levels of active caspase 3 and Bax by 50%, and a 90% increase in the ratio of Bcl-2/Bax, compared with the PBS-treated groups. These data suggested that Y-27632 protected retinal function by inhibiting the apoptosis of photoreceptor cells in the RCS rat model. The present study demonstrated for the first time, to the best of our knowledge, to report the use of Y-27632 for protection against RP in an RCS rat model. Y-27632 may be a potential candidate for the treatment of human RP.
机译：色素性视网膜炎（RP）是一种遗传性视网膜疾病，其特征是视杆和视锥光感受器变性。本研究旨在评估在皇家外科医学院（RCS）大鼠模型中玻璃体内注射Y-27632（Rho相关蛋白激酶（ROCK）的特异性抑制剂）对光感受器的保护作用。通过玻璃体内注射向RCS大鼠中施用不同浓度的Y-27632（1-50mM）。使用视网膜电图（ERG）记录Y-27632的作用，测量视网膜外核层（ONL）的厚度，并使用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色和Western blot分析检查凋亡标记。与1mM Y-27632处理过的Y27632相比，用10或50 mM的Y27632处理眼睛，导致ERG的a和b波振幅增加了30％，ONL厚度增加了10％。载体（磷酸盐缓冲盐水; PBS）处理的组。此外，用10 mM Y27632处理的眼睛的TUNEL阳性细胞减少90％，同时活性半胱天冬酶3和Bax的蛋白质表达水平降低50％，Bcl-2 / Bax比值增加90％与PBS处理组相比。这些数据表明Y-27632通过抑制RCS大鼠模型中的感光细胞凋亡来保护视网膜功能。据我们所知，本研究首次证明了在RCS大鼠模型中使用Y-27632预防RP的作用。 Y-27632可能是治疗人RP的潜在候选药物。

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