Retinitis pigmentosa (RP) is a heterogeneous group of retinal degenerative diseases in which the final pathological feature is photoreceptor cell apoptosis. Currently, the pathogenesis of RP remains poorly understood and therapeutics are ineffective. 17β-Oestradiol (βE2) is universally acknowledged as a neuroprotective factor in neurodegenerative diseases and has manifested neuroprotective effects in a light-induced retinal degeneration model. Recently, we identified N-myc downstream regulated gene 2 (NDRG2) suppression as a molecular marker of mouse retinal photoreceptor-specific cell death. βE2 has also been reported to regulate NDRG2 in salivary acinar cells. Therefore, in this study, we investigated whether βE2 plays a protective role in RP and regulates NDRG2 in photoreceptor cells. To this end, we generated RP models and observed that βE2 not only reduced the apoptosis of photoreceptor cells, but also restored the level of NDRG2 expression in RP models. Then, we showed that siNDRG2 inhibits the anti-apoptotic effect of βE2 on photoreceptor cells in a cellular RP model. Subsequently, we used a classic oestrogen receptor (ER) antagonist to attenuate the effects of βE2, suggesting that βE2 exerted its effects on RP models via the classic ERs. In addition, we performed a bioinformatics analysis, and the results indicated that the reported oestrogen response element (ERE) sequence is present in the promoter region of the mouse NDRG2 gene. Overall, our results suggest that βE2 attenuated the apoptosis of photoreceptor cells in RP models by maintaining NDRG2 expression via a classic ER-mediated mechanism.

色素性视网膜炎（RP）是视网膜退行性疾病的异质性组，其最终病理特征是感光细胞凋亡。目前，对RP的发病机理仍知之甚少，治疗方法无效。17β-雌二醇（βE2）被普遍认为是神经退行性疾病中的神经保护因子，并在光诱导的视网膜变性模型中表现出神经保护作用。最近，我们确定了N-myc下游调控基因2（NDRG2）抑制作为小鼠视网膜感光细胞特异性细胞死亡的分子标记。据报道，βE2可以调节唾液腺细胞中的NDRG2。因此，在这项研究中，我们调查了βE2是否在RP中起保护作用并调节感光细胞中的NDRG2。为此，我们建立了RP模型，观察到βE2不仅减少了感光细胞的凋亡，而且还恢复了RP模型中NDRG2的表达水平。然后，我们表明在细胞RP模型中，siNDRG2抑制βE2对感光细胞的抗凋亡作用。随后，我们使用经典的雌激素受体（ER）拮抗剂来减弱βE2的作用，表明βE2通过经典的ER对RP模型发挥作用。此外，我们进行了生物信息学分析，结果表明所报道的雌激素反应元件（ERE）序列存在于小鼠的启动子区域 我们发现在细胞RP模型中，siNDRG2抑制βE2对感光细胞的抗凋亡作用。随后，我们使用经典的雌激素受体（ER）拮抗剂来减弱βE2的作用，表明βE2通过经典的ER对RP模型发挥作用。此外，我们进行了生物信息学分析，结果表明所报道的雌激素反应元件（ERE）序列存在于小鼠的启动子区域 我们发现在细胞RP模型中，siNDRG2抑制βE2对感光细胞的抗凋亡作用。随后，我们使用经典的雌激素受体（ER）拮抗剂来减弱βE2的作用，表明βE2通过经典的ER对RP模型发挥作用。此外，我们进行了生物信息学分析，结果表明所报道的雌激素反应元件（ERE）序列存在于小鼠的启动子区域NDRG2基因。总体而言，我们的结果表明，βE2通过经典的ER介导的机制维持NDRG2表达，从而减弱了RP模型中感光细胞的凋亡。