Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK.
Genes (Basel). 2023 Jun 23;14(7):1325. doi: 10.3390/genes14071325.
is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific genes. Pathogenic variants involving cause a spectrum of retinopathies, including enhanced S-cone syndrome, Goldmann-Favre syndrome, retinitis pigmentosa, and clumped pigmentary retinal degeneration, with limited evidence of genotype-phenotype correlations. A common feature of -related disease is an abnormally high number of cone photoreceptors that are sensitive to short wavelength light, the S-cones. This characteristic has been supported by mouse studies, which have also revealed that loss of function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for -related retinopathies, there are a number of emerging therapeutic strategies under investigation, including the use of viral gene therapy and gene editing, that have shown promise for the future treatment of patients with variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies.
是一种核激素受体基因，对于视网膜杆状光感受器的正确发育是必需的。NR2E3 蛋白在杆状细胞前体中的表达抑制了锥细胞特异性基因的表达，并与包括 NRL 在内的其他转录因子协同作用，激活了杆状细胞特异性基因的表达。涉及的致病变体导致一系列视网膜病变，包括增强型 S- cone 综合征、Goldmann-Favre 综合征、色素性视网膜炎和聚集性色素性视网膜变性，基因型-表型相关性的证据有限。与相关疾病的一个共同特征是对短波长光敏感的圆锥体细胞数量异常增加，即 S- cone。这一特征得到了小鼠研究的支持，这些研究还表明，丧失功能会导致感光细胞发育为介于杆状细胞和锥状细胞之间的细胞。虽然目前尚无针对相关视网膜病变的有效治疗方法，但有许多新的治疗策略正在研究中，包括使用病毒基因治疗和基因编辑，这些策略为未来治疗患者的变体和其他遗传性视网膜疾病提供了希望。这篇综述详细概述了在正常发育和疾病中发挥作用的，以及相关的临床表型、动物模型和治疗研究。
