Regulation of rod gene expression has emerged as a potential therapeutic strategy to treat retinal degenerative diseases like retinitis pigmentosa (RP). We previously reported on a small molecule modulator of the rod transcription factor Nr2e3, Photoregulin1 (PR1), that regulates the expression of photoreceptor-specific genes. Although PR1 slows the progression of retinal degeneration in models of RP in vitro, in vivo analyses were not possible with PR1. We now report a structurally unrelated compound, Photoregulin3 (PR3) that also inhibits rod photoreceptor gene expression, potentially though Nr2e3 modulation. To determine the effectiveness of PR3 as a potential therapy for RP, we treated RhoP23H mice with PR3 and assessed retinal structure and function. PR3-treated RhoP23H mice showed significant structural and functional photoreceptor rescue compared with vehicle-treated littermate control mice. These results provide further support that pharmacological modulation of rod gene expression provides a potential strategy for the treatment of RP.

中文翻译：

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小分子 Photoregulin3 预防视网膜色素变性 RhoP23H 小鼠模型的视网膜变性

视杆基因表达的调控已成为治疗视网膜色素变性 (RP) 等视网膜退行性疾病的潜在治疗策略。我们之前报道了杆状转录因子 Nr2e3 的小分子调节剂 Photoregulin1 (PR1)，它调节光感受器特异性基因的表达。尽管 PR1 在体外 RP 模型中减缓了视网膜变性的进展，但 PR1 无法进行体内分析。我们现在报告了一种结构无关的化合物 Photoregulin3 (PR3)，它也可能通过 Nr2e3 调节抑制杆状光感受器基因表达。为了确定 PR3 作为 RP 潜在疗法的有效性，我们用 PR3 治疗 RhoP23H 小鼠并评估了视网膜结构和功能。与载体处理的同窝对照小鼠相比，PR3 处理的 RhoP23H 小鼠显示出显着的结构和功能光感受器拯救。这些结果进一步支持杆状基因表达的药理学调节为治疗 RP 提供了一种潜在的策略。