Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations.

Cell Death Dis

Division of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Published: September 2024

PRLΔE1, a retina-specific isoform of prolactin, is expressed in multiple and diverse forms of canine inherited retinal degeneration (IRD). We find that while PRLΔE1 expression in rods is not associated with the initial phase of disease characterized by acute photoreceptor cell death, it is associated with the protracted phase of slow cell loss. Restoration of photoreceptors to a healthy state by gene-specific replacement therapy of individual IRDs successfully suppresses PRLΔE1 expression. Moreover, short-term PRLΔE1 silencing using shRNA results in preservation of outer nuclear layer thickness, suggesting PRLΔE1 drives retinal disease. However, longer-term observations reveal off-target toxic effects of the PRLΔE1 shRNA, precluding determination of its full therapeutic potential. Future research efforts aimed at enhancing the safety and specificity of PRLΔE1-targeting strategies may identify a potential universal intervention strategy for sustaining photoreceptors during the prolonged phase of multiple IRDs.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410941PMC
http://dx.doi.org/10.1038/s41419-024-07070-1DOI Listing

Publication Analysis

Top Keywords

inherited retinal
8
prlΔe1 expression
8
prlΔe1
7
retinal
4
retinal prolactin
4
prolactin isoform
4
isoform prlΔe1
4
prlΔe1 sustains
4
sustains rod
4
rod disease
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!