{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sudharsan R"],"funding":["U.S. Department of Health & Human Services | NIH | National Eye Institute","NEI NIH HHS","Foundation Fighting Blindness","U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)","McCabe Fund Pilot Grant University Research Foundation, University of Pennsylvania","S.G.Jacobson MD PhD Memorial Fund Unrestricted funds from RPB","Foundation Fighting Blindness (Foundation Fighting Blindness, Inc.)"],"pagination":["682"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11410941"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(9)"],"pubmed_abstract":["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."],"journal":["Cell death & disease"],"pubmed_title":["Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations."],"pmcid":["PMC11410941"],"funding_grant_id":["R01 EY017549","NA","EY006855","R01 EY006855","R24 EY022012","EY017549"],"pubmed_authors":["Aguirre GD","Sumaroka A","Beltran WA","Sudharsan R","Swider M","Kwok J","Cideciyan AV"],"additional_accession":[]},"is_claimable":false,"name":"Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T11:44:25.431Z","creation":"2025-04-04T12:53:46.439Z"},"accession":"S-EPMC11410941","cross_references":{"pubmed":["39294136"],"doi":["10.1038/s41419-024-07070-1"]}}