Abstract
Purpose :
Our goal was to investigate the neuroprotective effects of galantamine, an FDA-approved mild Alzheimer’s Disease treatment, in a mouse model of blast-induced traumatic optic neuropathy.
Methods :
We exposed one eye of an anesthetized mouse to two bursts of over-pressurized air, 0.5 seconds apart for three days in a row. Blast and sham mice were given either regular or galantamine water (120mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electrophysiology and optical coherence tomography were performed 1 month after injury. Optic nerve and retina histology, ELISAs, TUNEL, Western blot, and immunohistochemistry were performed to assess oxidative stress, inflammation, cell death, and synaptic changes.
Results :
Galantamine treatment preserved visual function based on ERG and VEP. Injury did not affect the amax, however it significantly decreased the bmax from 246 ± 37 mV to 157 ± 41 mV. Galantamine treatment preserved the bmax to 198 ± 22 mV. Similarly, injury reduced the amplitude of the VEP N1 from 43 ± 10 mV to 26 ± 6.4 mV, which was ameliorated by galantamine treatment (36 ± 7.6 mV). Galantamine preserved retinal synaptic overlap in the outer plexiform layer based on immunolabeling of synaptophysin and calbindin-D or PKCα. Galantamine also prevented axon degeneration in the optic nerve. Further, galantamine preserved SOD2 levels and prevented blast-induced increases in IL-1α and IL-1β.
Conclusions :
Post-injury treatment with galantamine after injury is effective in protecting the retina and optic nerve and preserving vision. Galantamine may be a promising treatment for indirect traumatic optic neuropathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.