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Small Molecule Photoregulin3 Prevents Retinal Degeneration in the

Small Molecule Photoregulin3 Prevents Retinal Degeneration in the

Paul A Nakamura, Andy A Shimchuk, Shibing Tang, Zhizhi Wang, Kole DeGolier, Sheng Ding, Thomas A Reh

Elife. 2017 Nov 17;6:e30577.

PMID: 29148976

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 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP785708330	Photoregulin3		785708-33-0	Price

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