Enriched environment and visual stimuli protect the retinal pigment epithelium and photoreceptors in a mouse model of non-exudative age-related macular degeneration

DIEGUEZ, HERNÁN H; CALANNI JS; ROMEO, HORACIO E; ALAIMO, AGUSTINA; GONZÁLEZ FLEITAS, MARÍA F; IAQUINANDI, AGUSTINA; CHIANELLI, MÓNICA S; KELLER SARMIENTO, MARÍA I; SANDE, PABLO H; ROSENSTEIN, RUTH E; DORFMAN, DAMIÁN

Cell Death & Disease

Nature Pub Group

Lugar: London; Año: 2021

2041-4889

Non-exudativeage-related macular degeneration (NE-AMD) represents the leading cause ofblindness in the elderly. Currently, there are no available treatments forNE-AMD. We have developed a NE-AMD model induced by superior cervicalganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks.Several lines of evidence strongly support the involvement of oxidative stressin NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. We analysedthe effect of enriched environment (EE) and visual stimulation (VS) in theRPE/outer retina damage within experimental NE-AMD. Exposure to EE starting 48h post-SCGx, which had no effect on the ubiquitous choriocapillaris widening,protected visual functions, avoided Bruch´s membrane thickening, and the lossof RPE melanin content, melanosome number, and retinoid isomerohydrolase(RPE65)-immunoreactivity, as well as RPE and pdamage, ons, al ro content and melanosome number decrease,Brucherations induced by hotoreceptor ultrastructural damage, exclusivelycircumscribed to the central temporal (but not nasal) region, induced by experimentalNE-AMD. EE also prevented the increase in outer retina/RPE oxidative stressmarkers and decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, EE inducedan increase in RPE and retinal brain-derived neurotrophic factor (BDNF) levels,particularly in Müller cells. When EE exposure was delayed (dEE), starting at 4weeks post-SCGx, it restored visual functions and reversed the decrease in RPEmelanin content and RPE65-immunoreactivity. Exposing animals to VS protectedvisual functions and prevented the decrease in RPE melanin content andRPE65-immunoreactivity. These findings suggest that EE housing and visual stimulationcould become a promising therapeutic strategy for NE-AMD