Exploring single-cell RNA sequencing as a decision-making tool in the clinical management of Fuchs’ endothelial corneal dystrophy

IF 18.6 1区 医学 Q1 OPHTHALMOLOGY
Gink N. Yang , Yu B.Y. Sun , Philip Ke Roberts , Hothri Moka , Min K. Sung , Jesse Gardner-Russell , Layal El Wazan , Bridget Toussaint , Satheesh Kumar , Heather Machin , Gregory J. Dusting , Geraint J. Parfitt , Kathryn Davidson , Elaine W. Chong , Karl D. Brown , Jose M. Polo , Mark Daniell
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Abstract

Single-cell RNA sequencing (scRNA-seq) has enabled the identification of novel gene signatures and cell heterogeneity in numerous tissues and diseases. Here we review the use of this technology for Fuchs’ Endothelial Corneal Dystrophy (FECD). FECD is the most common indication for corneal endothelial transplantation worldwide. FECD is challenging to manage because it is genetically heterogenous, can be autosomal dominant or sporadic, and progress at different rates. Single-cell RNA sequencing has enabled the discovery of several FECD subtypes, each with associated gene signatures, and cell heterogeneity. Current FECD treatments are mainly surgical, with various Rho kinase (ROCK) inhibitors used to promote endothelial cell metabolism and proliferation following surgery. A range of emerging therapies for FECD including cell therapies, gene therapies, tissue engineered scaffolds, and pharmaceuticals are in preclinical and clinical trials. Unlike conventional disease management methods based on clinical presentations and family history, targeting FECD using scRNA-seq based precision-medicine has the potential to pinpoint the disease subtypes, mechanisms, stages, severities, and help clinicians in making the best decision for surgeries and the applications of therapeutics. In this review, we first discuss the feasibility and potential of using scRNA-seq in clinical diagnostics for FECD, highlight advances from the latest clinical treatments and emerging therapies for FECD, integrate scRNA-seq results and clinical notes from our FECD patients and discuss the potential of applying alternative therapies to manage these cases clinically.

探索将单细胞 RNA 测序作为福氏内皮性角膜营养不良症临床治疗的决策工具。
单细胞 RNA 测序(scRNA-seq)能够识别许多组织和疾病中的新型基因特征和细胞异质性。在此,我们回顾了该技术在福氏内皮性角膜营养不良症(FECD)中的应用。FECD 是全球最常见的角膜内皮移植适应症。福氏角膜内皮营养不良症具有遗传异质性,可能是常染色体显性遗传,也可能是散发性遗传,而且进展速度各不相同,因此治疗难度很大。单细胞 RNA 测序发现了几种 FECD 亚型,每种亚型都有相关的基因特征和细胞异质性。目前,FECD 的治疗方法主要是外科手术,手术后使用各种 Rho 激酶(ROCK)抑制剂来促进内皮细胞的新陈代谢和增殖。一系列针对 FECD 的新兴疗法,包括细胞疗法、基因疗法、组织工程支架和药物疗法,都已进入临床前和临床试验阶段。与基于临床表现和家族史的传统疾病管理方法不同,利用基于 scRNA-seq 的精准医疗来靶向 FECD 有可能准确定位疾病的亚型、机制、分期和严重程度,并帮助临床医生做出手术和治疗应用的最佳决策。在这篇综述中,我们首先讨论了在 FECD 临床诊断中使用 scRNA-seq 的可行性和潜力,重点介绍了 FECD 最新临床治疗方法和新兴疗法的进展,整合了 scRNA-seq 结果和 FECD 患者的临床记录,并讨论了应用替代疗法临床管理这些病例的潜力。
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来源期刊
CiteScore
34.10
自引率
5.10%
发文量
78
期刊介绍: Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.
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