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Y. Duan, J.L. Goldberg; Trophic Responsiveness of Retinal Ganglion Cells After Optic Nerve Injury . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4855.
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© ARVO (1962-2015); The Authors (2016-present)
Why do retinal ganglion cells (RGCs) die after injury? For example, by 48 hours after axotomy in postnatal rats, over 90% of retinal ganglion cells undergo apoptosis. Recent evidence suggests that RGCs die after axon injury for at least two reasons: they are cut off from target–derived trophic signals, and they lose their responsiveness to such signals. Responsiveness can be restored after axotomy by elevating levels of either electrical activity or cyclic AMP (cAMP). This raises the hypothesis that, after injury, neurons lose trophic responsiveness because they are less active, or less able to elevate cAMP in response to electrical activity, or both.
Here we use the postnatal rat retina and optic nerve as a model system to study the responsiveness of RGCs to trophic factors. Retinal waves were recorded using calcium imaging at different time points after axotomy, as a measure of electrical activity in RGCs. cAMP levels were monitored using a FRET–based genetically encoded cAMP sensor EPAC transfected into RGCs using both biolistic and in vivo electroporation approaches.
In the first 12 hours after axotomy, retinal activity is unchanged. Furthermore, injured RGCs maintain electrical activity identical in quantity and frequency to controls. Finally, we found that the FRET–based cAMP sensor can reliably measure changes in cAMP levels in RGCs in vitro and in explanted retinas.
RGCs do not decrease their levels of activity after optic nerve injury. We are currently investigating the dynamics of cAMP levels after axotomy. Understanding why RGCs lose responsiveness to trophic factors after axotomy will provide insights for promoting neuronal survival and axonal regeneration after injury.
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