Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa
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 p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/30577 |
| _version_ | 1811199444919517184 |
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| author | Paul A Nakamura Andy A Shimchuk Shibing Tang Zhizhi Wang Kole DeGolier Sheng Ding Thomas A Reh |
| author_facet | Paul A Nakamura Andy A Shimchuk Shibing Tang Zhizhi Wang Kole DeGolier Sheng Ding Thomas A Reh |
| author_sort | Paul A Nakamura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:48:11Z |
| format | Article |
| id | doaj.art-4d9c3696a19f4d4dbb4ba020da5ca70d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:48:11Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4d9c3696a19f4d4dbb4ba020da5ca70d2022-12-22T03:53:01ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.30577Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosaPaul A Nakamura0https://orcid.org/0000-0002-3845-8477Andy A Shimchuk1Shibing Tang2Zhizhi Wang3Kole DeGolier4Sheng Ding5Thomas A Reh6https://orcid.org/0000-0002-3524-0886Department of Biological Structure, University of Washington, School of Medicine, Seattle, United StatesDepartment of Biological Structure, University of Washington, School of Medicine, Seattle, United StatesDepartment of Pharmaceutical Chemistry, UCSF School of Pharmacy, University of California, San Francisco, San Francisco, United StatesDepartment of Biological Structure, University of Washington, School of Medicine, Seattle, United StatesDepartment of Biological Structure, University of Washington, School of Medicine, Seattle, United StatesDepartment of Pharmaceutical Chemistry, UCSF School of Pharmacy, University of California, San Francisco, San Francisco, United StatesDepartment of Biological Structure, University of Washington, School of Medicine, Seattle, United StatesRegulation 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.https://elifesciences.org/articles/30577retinal degenerationphotoreceptor dystrophyligand |
| spellingShingle | Paul A Nakamura Andy A Shimchuk Shibing Tang Zhizhi Wang Kole DeGolier Sheng Ding Thomas A Reh Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa eLife retinal degeneration photoreceptor dystrophy ligand |
| title | Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa |
| title_full | Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa |
| title_fullStr | Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa |
| title_full_unstemmed | Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa |
| title_short | Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa |
| title_sort | small molecule photoregulin3 prevents retinal degeneration in the rhop23h mouse model of retinitis pigmentosa |
| topic | retinal degeneration photoreceptor dystrophy ligand |
| url | https://elifesciences.org/articles/30577 |
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