Abstract
Purpose: :
Environmental enrichment (EE)isa combination of complex inanimate and social stimuli in which animals are reared in large groups and cages with toys, tunnels, nesting material and running wheels that are changed frequently. EE increases brain plasticity, accelerates neural development and slows down neuronal degeneration, partly through increased production of trophic factors. Because neurotrophins are protective for photoreceptors, we tested the hypothesis that early exposure to EE slows down photoreceptor degeneration in a mouse model of Retinitis Pigmentosa (RP) and prevents the decay of retinal structure and function.
Methods: :
Pregnant rd10 mutant mice and their litters were exposed to EE. Retinal structure and visual function of the offspring were assessed at P24, P45, P60 and P90. Controls were age-matched rd10 mice raised in standard (ST) laboratory conditions. Survival of photoreceptors was estimated measuring the outer nuclear layer thickness on retinal sections after fluorescent nuclear staining and confocal microscopy. The total number of cones/retina was estimated counting cones on whole mount retinas from age-matched EE and ST mice after Red-Green Opsin and Blue-Opsin antibody staining. Retinal morphology was studied with cell-type specific antibody staining and confocal microscopy. Retinal function was assessed with flash ERG recordings in photopic conditions. Finally, the visual system overall performance in photopic conditions was determined by measuring the visual acuity of mice with Prusky water maze.
Results: :
rd10 mice born in EE conditions display higher number of surviving photoreceptors than ST mice at all the time points tested. Cones appear greatly preserved even at P90, when no photoreceptors persist in the retina of rd10 mice raised in ST conditions. Retinal morphology is better retained as well. Cone-driven ERG responses can be recorded up to P60. Finally, visual behavior confirms greatly increased survival of cone-mediated vision in enriched mice. At P60 their visual acuity is close to that of wild type animals without retinal degeneration.
Conclusions: :
Exposure of rd10 mutant mice to EE decreases photoreceptor degeneration and preserves retinal structure and function. EE might represent a non invasive approach to enhance photoreceptor survival in inherited photoreceptor degeneration.
Keywords: retinal degenerations: cell biology • retinitis • visual acuity