Amin Dwarkesh, Kuwajima Takaaki
Department of Ophthalmology, The Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Front Ophthalmol (Lausanne). 2022 May 31;2:905352. doi: 10.3389/fopht.2022.905352. eCollection 2022.
Retinal ganglion cells (RGCs) are the neurons in the retina which directly project to the brain and transmit visual information along the optic nerve. Glaucoma, one of the leading causes of blindness, is characterized by elevated intraocular pressure (IOP) and degeneration of the optic nerve, which is followed by RGC death. Currently, there are no clinical therapeutic drugs or molecular interventions that prevent RGC death outside of IOP reduction. In order to overcome these major barriers, an increased number of studies have utilized the following combined analytical methods: well-established rodent models of glaucoma including optic nerve injury models and transcriptomic gene expression profiling, resulting in the successful identification of molecules and signaling pathways relevant to RGC protection. In this review, we present a comprehensive overview of pathological features in a variety of animal models of glaucoma and top differentially expressed genes (DEGs) depending on disease progression, RGC subtypes, retinal regions or animal species. By comparing top DEGs among those different transcriptome profiles, we discuss whether commonly listed DEGs could be defined as potential novel therapeutic targets in glaucoma, which will facilitate development of future therapeutic neuroprotective strategies for treatments of human patients in glaucoma.
视网膜神经节细胞(RGCs)是视网膜中的神经元,它们直接投射到大脑,并沿着视神经传递视觉信息。青光眼是导致失明的主要原因之一,其特征是眼压升高和视神经退化,随后是RGC死亡。目前,除了降低眼压外,没有临床治疗药物或分子干预措施能够预防RGC死亡。为了克服这些主要障碍,越来越多的研究采用了以下联合分析方法:成熟的青光眼啮齿动物模型,包括视神经损伤模型和转录组基因表达谱分析,从而成功鉴定出与RGC保护相关的分子和信号通路。在这篇综述中,我们全面概述了各种青光眼动物模型的病理特征,以及根据疾病进展、RGC亚型、视网膜区域或动物物种划分的顶级差异表达基因(DEGs)。通过比较这些不同转录组谱中的顶级DEGs,我们讨论了常见列出的DEGs是否可以被定义为青光眼潜在的新型治疗靶点,这将有助于为青光眼患者开发未来的治疗性神经保护策略。