Miller Annie L, James Rebekah E, Harvey Alan R, Trifunović Dragana, Carvalho Livia S
Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia.
Retinal Genomics and Therapy Laboratory, Lions Eye Institute, Nedlands, WA, Australia.
Front Cell Dev Biol. 2023 Aug 4;11:1224078. doi: 10.3389/fcell.2023.1224078. eCollection 2023.
Elucidation of the cellular changes that occur in degenerating photoreceptors of people with inherited retinal diseases (IRDs) has been a focus for many research teams, leading to numerous theories on how these changes affect the cell death process. What is clearly emerging from these studies is that there are common denominators across multiple models of IRD, regardless of the underlying genetic mutation. These common markers could open avenues for broad neuroprotective therapeutics to prevent photoreceptor loss and preserve functional vision. In recent years, the role of epigenetic modifications contributing to the pathology of IRDs has been a particular point of interest, due to many studies noting changes in these epigenetic modifications, which coincide with photoreceptor cell death. This review will discuss the two broad categories of epigenetic changes, DNA methylation and histone modifications, that have received particular attention in IRD models. We will review the altered epigenetic regulatory events that are believed to contribute to cell death in IRDs and discuss the therapeutic potential of targeting these alterations.
阐明遗传性视网膜疾病（IRD）患者退化的光感受器中发生的细胞变化一直是许多研究团队关注的焦点，由此产生了许多关于这些变化如何影响细胞死亡过程的理论。从这些研究中清晰显现的是，无论潜在的基因突变如何，在多种IRD模型中都存在共同特征。这些共同标记物可能为广泛的神经保护疗法开辟道路，以防止光感受器丧失并保留功能性视力。近年来，由于许多研究指出这些表观遗传修饰的变化与光感受器细胞死亡同时发生，因此表观遗传修饰在IRD病理学中的作用一直是特别关注的焦点。本综述将讨论两类受到特别关注的表观遗传变化，即DNA甲基化和组蛋白修饰，它们在IRD模型中受到了特别关注。我们将回顾那些被认为导致IRD细胞死亡的表观遗传调控事件的改变，并讨论针对这些改变的治疗潜力。
