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Viviana Guadagni, Elena Novelli, Enrica Strettoi; Environmental Enrichment reduces photoreceptor degeneration and retinal inflammation in a mouse model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4261.
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© ARVO (1962-2015); The Authors (2016-present)
In Retinitis Pigmentosa (RP), a genetic defect causes the primary degeneration of rods. Cones die secondarily, partly due to a locally hostile environment. Although microglial activation is known to occur, studies on the role of inflammation in RP pathogenesis have been undertaken only recently. We have previously shown that environmental enrichment (EE) creates a retinal milieu sustaining photoreceptor survival and delaying degeneration in rd10 mice, a model of RP. We now investigate whether beneficial effects of EE are associated to a reduction of the retinal inflammatory response in the same mutant.
rd10 mice were reared from birth in EE with enhanced motor, social and sensorial stimuli. Age-matched rd10 and wt C57Bl6/J mice kept in standard (ST) laboratory conditions were used as controls. At 45 days, animals were euthanized and the retinas dissected, flash frozen in cold isopenthane and stored at -80°C for molecular analysis. For histological studies, eyes (n=6 for each experimental group) were fixed in 4% PFA; retinal whole mounts or cryostat sections were stained with cell-specific antibodies for retinal neuronal types, macro and microglia, then imaged by confocal microscopy. For molecular studies, retinal RNA extraction and cDNA synthesis were conducted following the manufacturer’s protocol (QIAGEN). cDNAs were used to analyze the expression of cytokines and chemokines by RT-PCR, using arrays consisting of 84 GOIs and 12 controls (PAMM-150ZC, QIAGEN). A total of 9 mice/strain were used. Retinas of 3 mice for each group were pooled. Three arrays/group were analyzed.
Iba1 antibody staining showed a strong pattern of microglial activation in the outer retina of ST rd10 mice, a more moderate pattern in retinas of EE rd10 mice and virtually no activation in wt samples. RT-PCR followed by statistical analysis (Student t-test) showed in rd10 ST a widespread overexpression of inflammatory species with statistically significant upregulation (p< 0,05) in 14 out of 84 genes. These included Bmp2 and Ccl5. In EE samples this pattern was partially reverted toward the wt expression.
Environmental enrichment slows down inherited photoreceptor death concomitantly decreasing retinal inflammation and creating local conditions favorable to cell survival. Anti-inflammatory treatments should be considered as a therapeutic options for RP.
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