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E. Strettoi, I. Barone, E. Novellli; Environmental Enrichment Delays Photoreceptor Degeneration in a Mouse Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4052.
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© ARVO (1962-2015); The Authors (2016-present)
Enviromental enrichment (EE)isa combination of complex innimate 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. We tested the hypothesis that early exposure to EE could slow down photoreceptor degeneration in a mouse model of Retinitis Pigmentosa (RP).
Pregnant rd10 mutant mice and their litters were exposed to EE. Retinal structure of the offspring was assessed at P24, P45 and P60. Controls were age-matched rd10 mice raised in standard (ST) conditions.Survival of photoreceptors was estimated measuring ONL thickness on retinal sections after fluorescent nuclear staining and confocal microscopy. Pycnotic (condensed) nuclei from degenerating photoreceptors were counted in confocal images of the ONL of retinal whole mounts. For cone counts, retinas from age-matched EE and ST mice were stained with Red-Green Opsin and Blue-Opsin antibodies. Cone-rich and cone-poor areas were imaged by means of fluorescence digital pictures of retinal whole mounts and used to trace cone isodensity curves. Cone densities within each curve were estimated separately by automatically counting cones on high resolution confocal images. Local cone densities were then assigned to corresponding isodensity areas on retinal maps using a contour plot graph. The total number of cones/retina was then estimated.
rd10 mice born in EE conditions open their eyes 3 days earlier than ST counterparts. The number of pycnotic nuclei from dying photoreceptors in the ONL is lower in EE than in ST mice at P24 and P45. The number of surviving cones, on the contrary, is higher in retina of EE mice. An abrupt decrease in cone number occurs in the rd10 retina between P45 and P60 but it is strongly reduced by EE. At P60, an average of 80,000 intact cones, with elongated outer segments, persist in EE retinas, against only 40,000 dystrophic cones remaining in ST retinas. A higher number of rods, with outer segments still expressing the light-sensitive channel, is preserved as late as P45. Synaptic terminals of photoreceptors in the OPL of EE retinas are also maintained.
Exposure of rd10 mutant mice to EE decreases photoreceptor degeneration and promotes remarkable preservation of rods and cones up to 2 months of age. EE might represent a non invasive approach to enhance photoreceptor survival in inherited photoreceptor degeneration.
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