PDF(Pubmed)
Abstract：
NR2E3 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 NR2E3 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 NR2E3-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 Nr2e3 function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for NR2E3-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 NR2E3 variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of NR2E3 in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies.
摘要：
NR2E3是视网膜杆光感受器正确发育所需的核激素受体基因。NR2E3蛋白在杆状细胞前体中的表达抑制视锥细胞特异性基因的表达,与包括NRL在内的其他转录因子一致，激活杆特异性基因的表达。涉及NR2E3的致病变异导致一系列视网膜病变，包括强化S-锥综合征,Goldmann-Favre综合征,视网膜色素变性,色素性视网膜变性，基因型-表型相关性的证据有限。NR2E3相关疾病的一个共同特征是对短波长光敏感的视锥光感受器数量异常高，S-锥.这一特征得到了小鼠研究的支持，这也揭示了Nr2e3功能的丧失导致光感受器发育为介于杆和视锥之间的细胞。虽然目前尚无NR2E3相关视网膜病变的治疗方法，有许多正在研究的新兴治疗策略，包括使用病毒基因疗法和基因编辑，这对NR2E3变异和其他遗传性视网膜疾病患者的未来治疗显示出了希望。这篇综述详细概述了目前对NR2E3在正常发育和疾病中的作用的认识，以及相关的临床表型，动物模型,和治疗研究。
