Abstract
Purpose :
Retinal degeneration associated with retinal pigment epithelial (RPE) loss is a leading cause of visual impairment. EA-2351 is a novel small molecule that is being developed for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). In an in vitro GA model, EA-2351 promotes proliferation and maturation of human retinal pigment epithelial (RPE) cells, leading to wound repair. In this study we evaluated whether intravitreal EA-2351 can protect against RPE atrophy induced by intravenous sodium iodate (NaIO3) in rats in vivo.
Methods :
Long-Evans rats received intravenous NaIO3 to induce RPE atrophy. On the same day, they were randomly assigned 1:1 to receive weekly intravitreal injections of either EA-2351 or vehicle to both eyes during 4 consecutive weeks. Following treatment completion, animals underwent full field electroretinogram recordings as well as visual acuity (VA) assessments using Optomotry (CerebralMechanics), in a masked manner. Animals were sacrificed 7 weeks after the first treatment and histological analysis was performed to determinate the extent of the RPE wounded areas.
Results :
At 30 days from the RPE atrophy induction, EA-2351 treatment led to significantly improved a-wave amplitudes as well as scotopic and photopic b wave amplitudes compared to the vehicle controls. Visual acuity was also significantly improved in eyes treated with EA-2351 compared to vehicle controls. After 7 weeks of RPE atrophy, eyes treated with EA-2351 show a significant reduction in the RPE wounded area compared to eyes treated with vehicle.
Conclusions :
EA-2351 treatment led to significant reductions in the extent of RPE atrophy in a chemical induced animal model of RPE degeneration. EA-2351 also led to significant improvements in retinal and visual function.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.