Nanoceria protect retinal pigment epithelium in the light damaged retina

Purpose : Dry age-related macular degeneration (AMD) is the most common form of AMD, characterized by retinal pigment epithelium (RPE) dysfunction and death, associated to lipofuscin accumulation, photoreceptors death, autophagy alterations and vision loss. Despite its frequency, only palliative therapies are available. In order to search for improvements we investigated the development of the dry AMD in the light damaged (LD) model and tested the protective effects of cerium oxide nanoparticles (nanoceria). Methods : The dry features of AMD were investigated on Sprague Dawley albino rats exposed to bright light (1000 lux) for 3h, 6h, 9h, 12h, 24h and for 24h followed by 3 and 7 days of recovery, then compared to the healthy controls. The treatment was performed by nanoceria intravitreal injection (2 µl [1mM]) in both eyes 3 days before light exposure (for 24h). After 7 days from injury treated and untreated animals were compared. Oxidative stress was evaluated by acrolein fluorescence intensity on immunolabeled retinal cryosections and RPE was pointed out by anti-RPE65 immunofluorescence. Lipofuscin quantitation was performed by ImageJ software on retinal whole mounts images acquired by confocal microscopy. Autophagy was analysed by LC3B-II western blot. Results : The RPE was disrupted in the dorsal retina of LD rats starting 3 days after injury. LCB3-II was significantly increased after 24h of light exposure (p<0,05) and remained up-regulated after 7 days of recovery (p<0,05). We also observed lipofuscin accumulation over time and increased oxidative stress already detectable after 7 days of recovery. By nanoceria treatment oxidative stress was significantly reduced in the outer nuclear layer (p<0,01) and in the RPE (p<0,05) of the treated group. Accordingly the blood-retinal barrier was intact since the RPE was not affected and lipofuscin was significantly reduced in terms of number of granules (p<0,001) and percentage of occupied area (p<0,001). LCB3-II was down-regulated in the nanoceria-treated animals compared to the untreated ones (p<0,001). Conclusions : Our study demonstrates that cerium oxide nanoparticles protect the RPE and limit the dry features of AMD in the light-damaged model. On this basis we propose nanoceria as a new potential therapeutic agent for the dry form of AMD.