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.

中文翻译：

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探索单细胞 RNA 测序作为 Fuchs 内皮性角膜营养不良临床治疗的决策工具


单细胞 RNA 测序 (scRNA-seq) 能够识别多种组织和疾病中的新基因特征和细胞异质性。在此，我们回顾一下该技术在 Fuchs 内皮性角膜营养不良 (FECD) 中的应用。 FECD 是全世界角膜内皮移植最常见的适应症。 FECD 的治疗具有挑战性，因为它具有遗传异质性，可以是常染色体显性遗传或散发性，并且进展速度不同。单细胞 RNA 测序已经发现了几种 FECD 亚型，每种亚型都具有相关的基因特征和细胞异质性。目前的FECD治疗主要是手术治疗，使用各种Rho激酶（ROCK）抑制剂来促进手术后内皮细胞的代谢和增殖。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，正处于临床前和临床试验中。与基于临床表现和家族史的传统疾病管理方法不同，使用基于 scRNA-seq 的精准医疗针对 FECD 有可能查明疾病亚型、机制、阶段、严重程度，并帮助临床医生做出最佳手术决策和治疗方案。治疗学的应用。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 的最新临床治疗和新兴疗法的进展，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在临床上管理这些病例的潜力。