Pattabiraman Padmanabhan Paranji, Feinstein Valeria, Beit-Yannai Elie
Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 West Michigan Street, Indianapolis, IN 46202-5209, USA.
Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Antioxidants (Basel). 2023 Feb 7;12(2):405. doi: 10.3390/antiox12020405.
Oxidative stress (OS) on tissues is a major pathological insult leading to elevated intraocular pressure (IOP) and primary open-angle glaucoma (POAG). Aqueous humor (AH) produced by the non-pigmentary ciliary epithelium (NPCE) drains out via the trabecular meshwork (TM) outflow pathway in the anterior chamber. The exosomes are major constituents of AH, and exosomes can modulate the signaling events, as well as the responses of their target TM tissue. Despite the presence of molecular mechanisms to negate OS, oxidative damage directly, as well as indirectly, influences TM health, AH drainage, and IOP. We proposed that the expression of microRNA (miRNAs) carried by exosomes in the AH can be affected by OS, and this can modulate the pathways in target cells. To assess this, we subjected NPCE to acute and chronic OS (A-OS and C-OS), enriched miRNAs, performed miRNA microarray chip analyses, and miRNA-based gene targeting pathway prediction analysis. We found that various miRNA families, including miR27, miR199, miR23, miR130b, and miR200, changed significantly. Based on pathway prediction analysis, we found that these miRNAs can regulate the genes including , , , and serine/threonine-protein phosphatase2A (). We propose that OS on the NPCE exosomal miRNA cargo can modulate the functionality of the TM tissue.
组织上的氧化应激（OS）是导致眼内压（IOP）升高和原发性开角型青光眼（POAG）的主要病理损伤。非色素睫状上皮（NPCE）产生的房水（AH）通过前房中的小梁网（TM）流出途径排出。外泌体是房水的主要成分，外泌体可以调节信号转导事件及其靶标TM组织的反应。尽管存在消除氧化应激的分子机制，但氧化损伤直接或间接影响TM健康、房水引流和眼内压。我们提出，房水中外泌体携带的微小RNA（miRNA）的表达会受到氧化应激的影响，这可以调节靶细胞中的信号通路。为了评估这一点，我们对NPCE进行急性和慢性氧化应激（A-OS和C-OS）处理，富集miRNA，进行miRNA微阵列芯片分析和基于miRNA的基因靶向信号通路预测分析。我们发现包括miR27、miR199、miR23、miR130b和miR200在内的各种miRNA家族发生了显著变化。基于信号通路预测分析，我们发现这些miRNA可以调节包括、、和丝氨酸/苏氨酸蛋白磷酸酶2A（）在内的基因。我们提出，NPCE外泌体miRNA负载上的氧化应激可以调节TM组织的功能。
