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Displacement of PDE4D3 with an anchoring disruptor peptide is RGC protective after injury

GSE260952 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/08/28 Platform GPL21103
Summary
Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased cAMP signaling in RGCs is neuroprotective, as has been previously demonstrated in multiple animal models, including optic nerve crush (ONC) injury. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear protein kinase A activity in cultured neurons and RGC survival in vivo after ONC injury. To explore potential mechanisms by which 4D3(E) expression promotes neuroprotection, mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq) for changes in RGC gene expression. 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.
Published in
Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide
Zhu Y, Nair RV, Xia X et al. · Experimental eye research 2024 · PMID 39097072 · doi:10.1016/j.exer.2024.110017
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Also filed as BioProject PRJNA1084724 and SRA study SRP493590. Searching any of these in the dataset finder brings you back here.

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