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Editors Selection IGR 9-2
Basic Science: Oxidative Stress in the ONH
Comment by Makoto Aihara on:
76536 Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes, Shim MS; Kim KY; Bu JH et al., Cell Death and Disease, 2018; 9: 285
It is shown that cAMP/PKA pathway activation exacerbates ONH astrocyte dysfunction induced by oxidative stress. Suppression of cAMP/PKA activation rescues astrocyte dysfunction via AKT phosphorylation. Oxidative stress itself tended to decrease cAMP/PKA activation to protect astrocyte. In addition, elevated cAMP is shown to enhance TNFalpha from astrocyte, leading to astrocyte dysfunction and axon damage. Taken together, modulation of cAMP/PKA pathway may be effective to protect ONH astrocytes and axons. Thus, the authors suggest that inhibition of this pathway is one of the targets for glaucoma therapy.
Inhibition of the cAMP/PKA pathway may be effective to protect ONH astrocytes and axons
The involvement of this pathway in ONH is a complicated but interesting story. This result is fully supported by the in vitro assays in detail. In the in vivo study on astrocyte dysfunction, the DBA2J glaucoma model was used, and degenerative astrocyte and axon loss in ONH were shown by SBEM images. In POAG, pressure stress at ONH promotes lamina deformation leading to a reduction in axoplasmic flow and capillary blood flow. Thus, oxidative stress-induced ONH astrocyte dysfunction may accelerate RGC axon damage. Although modulation of cAMP may be partially effective to suppress ONH astrocyte dysfunction, lowering the IOP remains the first line of treatment. The pathogenesis of ONH deformation is complicated. In addition to oxidative stress, the effect of shear stress on cAMP/PKA signaling should be examined in ONH astrocyte. Investigating how to modulate the cAMP/PKA pathway in a glaucoma model would be the next step. Needless to say, determining the timing of modulation and the methods of drug delivery is also important.
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