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Abstract #76536 Published in IGR 19-3
Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes
Shim MS; Kim KY; Bu JH; Nam HS; Jeong SW; Park TL; Ellisman MH; Weinreb RN; Ju WKCell Death and Disease 2018; 9: 285
See also comment(s) by Makoto Aihara •
Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration.
Hamilton Glaucoma Center and Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA.
Full articleClassification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
