Ibuprofen attenuates photoreceptor degeneration in light damage and retinitis pigmentosa mouse models

Abstract

Purpose : Patients with age-related macular degeneration (AMD) and retinitis pigmentosa (RP) demonstrate progressive degeneration of photoreceptor (PR) cells. The cause and mechanism of AMD and RP remain incompletely understood. Light damage (LD) is a commonly used acute retina degeneration model while the retinal degeneration 10 (rd10) mouse is a genetic model of retinitis pigmentosa. As ibuprofen(IBU), a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used to relieve pain, fever, and inflammation, has been reported to be neuroprotective in some model systems, we explored its potential retinal neuroprotective activity in LD and rd10 models.

Methods : Female BALB/cJ mice (10-week-old, Jackson Lab) were administered 200 mg/kg ibuprofen sodium salt by daily intraperitoneal (IP) injection starting three days prior to LD and post LD up to day 5(8 IP injections in total). Mice were dark-adapted for 12h before exposure to ~4000 lux cool fluorescent light for 4 h (n=8). Rd10 mice were IP injected with 200 mg/kg IBU every day starting from day 12 until day 35(n=8, breeding pairs from Jackson Lab). Spectral-domain optical coherence tomography (SD-OCT) were used to measure the retinal thickness and electroretinography (ERG) were used for functional analysis.

Results : In the vehicle injected animals, retinal outer nuclear layer (ONL) thickness was 10 ± 4.3% two weeks post LD(compared to untreated retinas) , and a-wave and B-wave maximal amplitudes were 22.8 ± 8.6% and 30.3 ± 14.2% respectively. In the animals injected with IBU, ONL thickness in the central region of the mouse retina was 71.1 ± 5.1% (P<0.001). A-wave and b-wave maximal amplitudes were also significantly preserved in IBU treated animals (52.4 ± 9.7% and 78.1 ± 15.3%; P<0.001). IBU also showed partial PR neuroprotection in the rd10 model. ONL thickness in the IBU-treated group on day 21 was 96.5 ± 5.1% thickness compared to that on day 14, while the vehicle group showed 82.5% of ONL thickness (P<0.001). Gene expression and immunohistochemical analyses of the study animals are in process.

Conclusions : Administration of the ibuprofen partially protects mouse retinas from light damage and delays ONL thinning in the rd10 mouse RP model. These findings suggest that the light damage and rd10 mouse models may share some mechanistic similarities and that NSAID may be a promising therapeutic approach for the retinal degenerative diseases.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.