Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
18 Sep 2024
18 Sep 2024
Historique:
received:
20
12
2023
accepted:
12
09
2024
revised:
03
09
2024
medline:
19
9
2024
pubmed:
19
9
2024
entrez:
18
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39294136
doi: 10.1038/s41419-024-07070-1
pii: 10.1038/s41419-024-07070-1
doi:
Substances chimiques
Prolactin
9002-62-4
Protein Isoforms
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
682Subventions
Organisme : Foundation Fighting Blindness (Foundation Fighting Blindness, Inc.)
ID : NA
Organisme : Foundation Fighting Blindness (Foundation Fighting Blindness, Inc.)
ID : NA
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : EY006855
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : EY006855
Organisme : U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
ID : EY017549
Informations de copyright
© 2024. The Author(s).
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