Retinal Prolactin Isoform PRLΔE1: A Key Player in Inherited Retinal Degenerations

Summary: A study published in Cell Death and Disease investigates the role of PRLΔE1, a retina-specific isoform of prolactin, in inherited retinal degenerations (IRDs). Key findings include:

1. PRLΔE1 is expressed in multiple canine models of IRD, specifically in diseased rod photoreceptors.
2. Its expression is associated with the protracted phase of slow cell loss rather than acute photoreceptor death.
3. PRLΔE1 expression is suppressed when photoreceptors are restored to a healthy state through gene-specific replacement therapy.
4. Short-term PRLΔE1 silencing using shRNA resulted in preservation of outer nuclear layer thickness, suggesting a potential therapeutic target.
5. However, longer-term observations revealed off-target toxic effects of the PRLΔE1 shRNA, limiting its immediate therapeutic potential.

This research provides new insights into the molecular mechanisms of IRDs and suggests PRLΔE1 as a potential universal intervention target for sustaining photoreceptors during the prolonged phase of multiple IRDs.

Reference: Sudharsan, R., Kwok, J., Swider, M., Sumaroka, A., Aguirre, G.D., Cideciyan, A.V., & Beltran, W.A. (2024). Retinal prolactin isoform PRLΔE1 sustains rod disease in inherited retinal degenerations. Cell Death and Disease, 15, 682. https://doi.org/10.1038/s41419-024-07070-1

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Hashtags:#InheritedRetinalDegeneration #PRLΔE1 #Photoreceptors #RetinalDisease #GeneTherapy #OcularResearch