Small molecule Photoregulin3 prevents retinal degeneration in the <i>Rho<sup>P23H</sup></i> mouse model of retinitis pigmentosa.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29148976.
- Also identified by DOI 10.7554/eLife.30577 and PMC identifier 5693111.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>Rho<sup>P23H</sup></i> mice with PR3 and assessed retinal structure and function. PR3-treated <i>Rho<sup>P23H</sup></i> 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.
Medical subject headings
- Gene Expression Regulation
- Orphan Nuclear Receptors
- Retinitis Pigmentosa