Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders

Christian T. Rutan Woods, Mustafa S. Makia, Tylor R. Lewis, Ryan Crane, Stephanie Zeibak, Paul Yu, Mashal Kakakhel, Carson M. Castillo, Vadim Y. Arshavsky, Muna I. Naash () and Muayyad R. Al-Ubaidi ()
Additional contact information
Christian T. Rutan Woods: University of Houston
Mustafa S. Makia: University of Houston
Tylor R. Lewis: Department of Ophthalmology, Duke University Medical Center
Ryan Crane: University of Houston
Stephanie Zeibak: University of Houston
Paul Yu: University of Houston
Mashal Kakakhel: University of Houston
Carson M. Castillo: Department of Ophthalmology, Duke University Medical Center
Vadim Y. Arshavsky: Department of Ophthalmology, Duke University Medical Center
Muna I. Naash: University of Houston
Muayyad R. Al-Ubaidi: University of Houston

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Given the absence of approved treatments for pathogenic variants in Peripherin-2 (PRPH2), it is imperative to identify a universally effective therapeutic target for PRPH2 pathogenic variants. To test the hypothesis that formation of the elongated discs in presence of PRPH2 pathogenic variants is due to the presence of the full complement of rhodopsin in absence of the required amounts of functional PRPH2. Here we demonstrate the therapeutic potential of reducing rhodopsin levels in ameliorating disease phenotype in knockin models for p.Lys154del (c.458-460del) and p.Tyr141Cys (c.422 A > G) in PRPH2. Reducing rhodopsin levels improves physiological function, mitigates the severity of disc abnormalities, and decreases retinal gliosis. Additionally, intravitreal injections of a rhodopsin-specific antisense oligonucleotide successfully enhance the physiological function of photoreceptors and improves the ultrastructure of discs in mutant mice. Presented findings shows that reducing rhodopsin levels is an effective therapeutic strategy for the treatment of inherited retinal degeneration associated with PRPH2 pathogenic variants.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48846-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48846-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48846-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().