TY - JOUR TI - Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa AU - Nakamura, Paul A AU - Shimchuk, Andy A AU - Tang, Shibing AU - Wang, Zhizhi AU - DeGolier, Kole AU - Ding, Sheng AU - Reh, Thomas A A2 - Nathans, Jeremy VL - 6 PY - 2017 DA - 2017/11/17 SP - e30577 C1 - eLife 2017;6:e30577 DO - 10.7554/eLife.30577 UR - https://doi.org/10.7554/eLife.30577 AB - 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. KW - retinal degeneration KW - photoreceptor dystrophy KW - ligand JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -