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激活 RASA1 信号通路增强晶状体诱导性近视豚鼠脉络膜组织细胞凋亡。

Enhanced Apoptosis in Choroidal Tissues in Lens-Induced Myopia Guinea Pigs by Activating the RASA1 Signaling Pathway.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, China.

Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Invest Ophthalmol Vis Sci. 2022 Oct 3;63(11):5. doi: 10.1167/iovs.63.11.5.

Abstract

PURPOSE

This study aimed to explore the role of the RAS p21 protein activator 1 (RASA1) signaling pathway in apoptosis in choroid tissues from guinea pigs with negative lens-induced myopia (LIM).

METHODS

Biometric measurements were performed to examine refractive status, ocular parameters, and choroidal thickness (ChT) after myopia induction. The choroidal morphology was observed by hematoxylin and eosin (H&E) staining and TUNEL assay. The expression of the RASA1 signaling pathway at the mRNA and protein levels in choroidal tissues was measured by real-time quantitative PCR (qPCR) and western blot assays.

RESULTS

Compared with the normal control (NC) group, the ocular length of the guinea pigs in LIM increased remarkably, as did the myopic refraction. ChT decreased after myopia induction. H&E staining showed that the thickness and laxity of the choroidal tissues in LIM were strikingly reduced. The number of apoptotic cells in the LIM eyes was increased. Moreover, qPCR and western blot assays showed that the expression levels of both RASA1 and BCL-2-associated agonist of cell death (BAD) were higher in the LIM group than in the NC group, whereas the expression level of B-cell lymphoma 2 (BCL-2) was decreased after 2 weeks of experimental myopia. However, the trend of RASA1, BAD, and BCL-2 expression was reversed after 4 weeks of experimental myopia compared with levels after 2 weeks of experimental myopia.

CONCLUSIONS

Results showed that the RASA1 signaling pathway is activated in choroid tissues in myopic guinea pigs. Activated RASA1 signaling induces high BAD expression and low BCL-2 expression, which in turn promotes apoptosis and ultimately causes ChT thinning in myopic guinea pigs.

摘要

目的

本研究旨在探讨 RAS p21 蛋白激活物 1(RASA1)信号通路在负透镜诱导性近视(LIM)豚鼠脉络膜组织细胞凋亡中的作用。

方法

进行生物测量以检查屈光度、眼参数和脉络膜厚度(ChT)在近视诱导后的变化。通过苏木精和伊红(H&E)染色和 TUNEL 检测观察脉络膜形态。通过实时定量 PCR(qPCR)和 Western blot 检测测量脉络膜组织中 RASA1 信号通路的 mRNA 和蛋白水平的表达。

结果

与正常对照组(NC)相比,LIM 组豚鼠眼轴长度显著增加,近视屈光度也显著增加。近视诱导后 ChT 减少。H&E 染色显示 LIM 脉络膜组织的厚度和松弛度明显降低。LIM 眼的凋亡细胞数量增加。此外,qPCR 和 Western blot 检测显示,与 NC 组相比,LIM 组 RASA1 和 BCL-2 相关细胞死亡激动剂(BAD)的表达水平均升高,而在实验性近视 2 周后 B 细胞淋巴瘤 2(BCL-2)的表达水平降低。然而,与实验性近视 2 周后的水平相比,在实验性近视 4 周后,RASA1、BAD 和 BCL-2 表达的趋势发生逆转。

结论

结果表明,RASA1 信号通路在近视豚鼠的脉络膜组织中被激活。激活的 RASA1 信号通路诱导高 BAD 表达和低 BCL-2 表达,进而促进凋亡,最终导致近视豚鼠的 ChT 变薄。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b7c/9578543/e1454fc7f809/iovs-63-11-5-f001.jpg

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