Abstract
Purpose :
Current approaches to treatment of nonarteritic anterior ischemic optic neuropathy (NAION) rely on early retinal ganglion cell (RGC) neuroprotection. However, current neuroprotective approaches have been ineffective when administered late (>1d) after induction in rodent and primate NAION models. We report on the success of a new neuroregenerative approach using TXA127 in rodent NAION (rNAION); a drug being utilized for human treatment of COVID complications.
Methods :
rNAION was unilaterally induced in anesthetized Long-Evans rats (250-300g) using intravenous rose bengal dye followed by induction with 11 seconds of a 532nm laser light (50mW power at eye; 500um spot size). One day post-induction, threshold animals (>500um mean optic nerve head edema) were implanted with 2ML4 Alzet pumps to deliver either TXA127 or vehicle (PBS) for 28 days. Animals were allowed to recover and visual acuity was measured by optomotry at 21-28 days post-induction . Following optomotry, animals were implanted with transcranial electrodes that did not penetrate the dura, allowed to recover for one week, and then evaluated for optic nerve function using flash visual evoked potentials (fVEP). Following euthanasia, tissue was obtained and evaluated for RGC quantification using stereology.
Results :
TXA127 administration improved both visual acuity (as measured by optomotry) and optic nerve function as measured by fVEP, compared with vehicle. This effect was seen even after treatment was begun at least 1 day post-induction. The animals with the most severe edema seemed to gain the most benefit. Effects were statistically significant using ANOVA.
Conclusions :
TXA127 appears to be an effective neuroregenerative treatment that can be utilized even when administered at times distant from the ischemic lesion induction. Current work is being done to further assess both the relative RGC survival and optic nerve neuroinflammatory responses to the drug.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.