Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide.
Exp Eye Res
; 246: 110017, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39097072
ABSTRACT
Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. 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 cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study 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). 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinal Ganglion Cells
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Optic Nerve Injuries
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Exp Eye Res
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: