Casey Eye Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Casey Eye Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Exp Eye Res. 2023 Mar;228:109367. doi: 10.1016/j.exer.2022.109367. Epub 2023 Feb 3.
Glaucoma is often associated with elevated intraocular pressure (IOP), generally due to obstruction of aqueous humor outflow within the trabecular meshwork (TM). Despite many decades of research, the molecular cause of this obstruction remains elusive. To study IOP regulation, several in vitro models, such as perfusion of anterior segments or mechanical stretching of TM cells, have identified several IOP-responsive genes and proteins. While these studies have proved informative, they do not fully recapitulate the in vivo environment where IOP is subject to additional factors, such as circadian rhythms. Thus, rodent animal models are now commonly used to study IOP-responsive genes in vivo. Several single-cell RNAseq studies have been performed where angle tissue, containing cornea, iris, ciliary body tissue in addition to TM, is dissected. However, it is advantageous to physically separate TM from other tissues because the ratio of TM cells is relatively low compared to the other cell types. In this report, we describe a new technique for rat TM microdissection. Evaluating tissue post-dissection by histology and immunostaining clearly shows successful removal of the TM. In addition, TaqMan PCR primers targeting biomarkers of trabecular meshwork (Myoc, Mgp, Chi3l1) or ciliary body (Myh11, Des) genes showed little contamination of TM tissue by the ciliary body. Finally, pitfalls encountered during TM microdissection are discussed to enable others to successfully perform this microsurgical technique in the rat eye.
青光眼通常与眼内压升高(IOP)有关,通常是由于小梁网(TM)内房水流出受阻所致。尽管经过了几十年的研究,但这种阻塞的分子原因仍然难以捉摸。为了研究 IOP 调节,几种体外模型,如前段灌注或 TM 细胞的机械拉伸,已经鉴定出几种 IOP 反应基因和蛋白质。虽然这些研究提供了有价值的信息,但它们并没有完全再现体内环境,在体内环境中,IOP 还受到其他因素的影响,如昼夜节律。因此,现在通常使用啮齿动物动物模型来研究体内的 IOP 反应基因。已经进行了几项单细胞 RNAseq 研究,其中包括解剖包含角膜、虹膜、睫状体组织的角组织,除了 TM。然而,将 TM 与其他组织物理分离是有利的,因为与其他细胞类型相比,TM 细胞的比例相对较低。在本报告中,我们描述了一种大鼠 TM 微解剖的新技术。通过组织学和免疫染色评估组织后,清楚地显示出 TM 的成功去除。此外,针对小梁网(Myoc、Mgp、Chi3l1)或睫状体(Myh11、Des)基因的 TaqMan PCR 引物显示,TM 组织受睫状体的污染很小。最后,讨论了在 TM 微解剖过程中遇到的陷阱,以使其他人能够在大鼠眼睛中成功地进行这种显微外科技术。