Abstract
Purpose :
Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are characterized by progressive degeneration of photoreceptor (PR) cells. The cause and mechanism of AMD and RP remain incompletely understood. Light damage is a commonly used acute retina degeneration model while retinal degeneration 10 (rd10) mice are a genetic model of retinitis pigmentosa. We previously showed that the mixed-kinase inhibitor SBJ-051 can protect mouse PRs from light damage induced PR injury and cell death (Kim et al., ARVO, 2017, 2019). Here we further define the neuroprotective activity of SBJ-051 in light damaged retinas and also show that it can attenuate PR degeneration in rd10 mice.
Methods :
Female BALB/cJ mice (10-week old) were administered 20 mg/kg SBJ-051 by daily intraperitoneal (IP) injection starting either 48 h prior to LD or post LD up to 72 h. Mice were dark-adapted for 12h before exposure to ~4000 lux cool fluorescent light for 4 h, followed by dark recovery for 16h. Rd10 mice (Jackson lab) were injected IP with 20 mg/kg SBJ-051 every other day starting from day 12 until day 35.
Results :
In the vehicle injected animals, retinal outer nuclear layer (ONL) thickness decreased 86.5 ± 6.6% two weeks post LD based on SD-OCT. In the animals injected IP with SBJ-051 starting prior to LD, there were no statistically significant changes in ONL thickness post LD. In the animals receiving SB-051 starting post LD (14h), ONL thickness only decreased 7.6 ± 4.5%. A-wave and b-wave maximal amplitudes were also significantly preserved with SBJ-051 treatment post LD (a-wave: 70.2 ± 9.7%, b-wave: 64.5 ± 15.3%; P<0.05). Preliminary data suggests that SBJ-05 can also partially protect PRs in the rd10 model. ONL thickness in the SBJ-051-treated group on day 28 showed 48.5 ± 3.9% thickness compared to that on day 14, while the vehicle group showed 25.5% of ONL thickness (P<0.05). Electroretinogram (ERG) and immunohistochemical analysis of rd10 mice are in process.
Conclusions :
Administration of the kinase inhibitor SBJ-051 either before or after LD protects mouse retinas from photochemical damage and attenuates ONL thinning in the rd10 mouse RP model. These findings suggest that PR protection through treatment with SBJ-051, or a related molecule, may be a promising therapeutic strategy for human retinal degeneration.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.