Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, 200080, China.
Exp Eye Res. 2023 Jun;231:109489. doi: 10.1016/j.exer.2023.109489. Epub 2023 Apr 20.
Retinal diseases remain among the leading causes of visual impairment in developed countries, despite great efforts in prevention and early intervention. Due to the limited efficacy of current retinal therapies, novel therapeutic methods are urgently required. Over the past two decades, advances in next-generation sequencing technology have facilitated research on RNA modifications, which can elucidate the relevance of epigenetic mechanisms to disease. N6-methyladenosine (m6A), formed by methylation of adenosine at the N6-position, is the most widely studied RNA modification and plays an important role in RNA metabolism. It is dynamically regulated by writers (methyltransferases) and erasers (demethylases), and recognized by readers (m6A binding proteins). Although the discovery of m6A methylation can be traced back to the 1970s, its regulatory roles in retinal diseases are rarely appreciated. Here, we provide an overview of m6A methylation, and discuss its effects and possible mechanisms on retinal diseases, including diabetic retinopathy, age-related macular degeneration, retinoblastoma, retinitis pigmentosa, and proliferative vitreoretinopathy. Furthermore, we highlight potential agents targeting m6A methylation for retinal disease treatment and discuss the limitations and challenges of research in the field of m6A methylation.
视网膜疾病仍然是发达国家视力障碍的主要原因之一,尽管在预防和早期干预方面做出了巨大努力。由于目前的视网膜治疗方法效果有限,因此迫切需要新的治疗方法。在过去的二十年中,下一代测序技术的进步促进了对 RNA 修饰的研究,这可以阐明表观遗传机制与疾病的相关性。N6-甲基腺苷(m6A)是由腺苷在 N6 位的甲基化形成的,是研究最多的 RNA 修饰之一,在 RNA 代谢中发挥重要作用。它由作家(甲基转移酶)和橡皮擦(去甲基酶)动态调节,并由读者(m6A 结合蛋白)识别。尽管 m6A 甲基化的发现可以追溯到 20 世纪 70 年代,但它在视网膜疾病中的调节作用很少被认识到。在这里,我们概述了 m6A 甲基化,并讨论了其对包括糖尿病视网膜病变、年龄相关性黄斑变性、视网膜母细胞瘤、视网膜色素变性和增生性玻璃体视网膜病变在内的视网膜疾病的影响及其可能的机制。此外,我们还强调了针对 m6A 甲基化治疗视网膜疾病的潜在靶向药物,并讨论了该领域 m6A 甲基化研究的局限性和挑战。