Department of Ophthalmology & Vision Science, University of Arizona College of Medicine-Tucson, Tucson, AZ 85711, USA.
Retina Specialists of Southern Arizonam, Tucson, AZ 85712, USA.
Genes (Basel). 2023 Feb 5;14(2):417. doi: 10.3390/genes14020417.
The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events in retinal development, aging, and degeneration. Epigenetic signaling regulates retinal progenitor (RPC) cell cycle exit during retinal laminar development, giving rise to retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, photoreceptors, and Müller glia. Age-related epigenetic changes such as DNA methylation in the retina and optic nerve are accelerated in pathogenic conditions such as glaucoma and macular degeneration, but reversing these epigenetic marks may represent a novel therapeutic target. Epigenetic writers also integrate environmental signals such as hypoxia, inflammation, and hyperglycemia in complex retinal conditions such as diabetic retinopathy (DR) and choroidal neovascularization (CNV). Histone deacetylase (HDAC) inhibitors protect against apoptosis and photoreceptor degeneration in animal models of retinitis pigmentosa (RP). The epigenome represents an intriguing therapeutic target for age-, genetic-, and neovascular-related retinal diseases, though more work is needed before advancement to clinical trials.
表观基因组代表了一个庞大的分子机制，它可以在不改变 DNA 碱基对序列本身的情况下，对 DNA 和组蛋白密码进行写入、读取和擦除化学修饰。分子测序技术的最新进展表明，表观遗传染色质标记直接介导了视网膜发育、衰老和变性过程中的关键事件。表观遗传信号调节视网膜祖细胞（RPC）细胞在视网膜层状发育过程中的细胞周期退出，从而产生视网膜神经节细胞（RGC）、无长突细胞、水平细胞、双极细胞、光感受器和 Müller 胶质细胞。与年龄相关的表观遗传变化，如视网膜和视神经中的 DNA 甲基化，在青光眼和黄斑变性等致病条件下加速，但逆转这些表观遗传标记可能代表一种新的治疗靶点。表观遗传写入器还整合了缺氧、炎症和高血糖等环境信号，在糖尿病视网膜病变（DR）和脉络膜新生血管（CNV）等复杂的视网膜疾病中。组蛋白去乙酰化酶（HDAC）抑制剂可防止色素性视网膜炎（RP）动物模型中的细胞凋亡和光感受器变性。尽管在临床试验前还需要做更多的工作，但表观基因组是一个有趣的与年龄、遗传和新生血管相关的视网膜疾病的治疗靶点。
