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

Authors :
Hernán H. Dieguez
Juan S. Calanni
Horacio E. Romeo
Agustina Alaimo
María F. González Fleitas
Agustina Iaquinandi
Mónica S. Chianelli
María I. Keller Sarmiento
Pablo H. Sande
Ruth E. Rosenstein
Damián Dorfman
Source :
Cell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

Abstract

Abstract Non-exudative age-related macular degeneration (NE-AMD), the main cause of blindness in people above 50 years old, lacks effective treatments at the moment. We have developed a new NE-AMD model through unilateral superior cervical ganglionectomy (SCGx), which elicits the disease main features in C57Bl/6J mice. The involvement of oxidative stress in the damage induced by NE-AMD to the retinal pigment epithelium (RPE) and outer retina has been strongly supported by evidence. We analysed the effect of enriched environment (EE) and visual stimulation (VS) in the RPE/outer retina damage within experimental NE-AMD. Exposure to EE starting 48 h post-SCGx, which had no effect on the choriocapillaris ubiquitous thickness increase, protected visual functions, prevented the thickness increase of the Bruch’s membrane, and the loss of the melanin of the RPE, number of melanosomes, and retinoid isomerohydrolase (RPE65) immunoreactivity, as well as the ultrastructural damage of the RPE and photoreceptors, exclusively circumscribed to the central temporal (but not nasal) region, induced by experimental NE-AMD. EE also prevented the increase in outer retina/RPE oxidative stress markers and decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, EE increased RPE and retinal brain-derived neurotrophic factor (BDNF) levels, particularly in Müller cells. When EE exposure was delayed (dEE), starting at 4 weeks post-SCGx, it restored visual functions, reversed the RPE melanin content and RPE65-immunoreactivity decrease. Exposing animals to VS protected visual functions and prevented the decrease in RPE melanin content and RPE65 immunoreactivity. These findings suggest that EE housing and VS could become an NE-AMD promising therapeutic strategy.

Subjects

Subjects :
Cytology
QH573-671

Details

Language :
English
ISSN :
20414889 and 93724357
Volume :
12
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Cell Death and Disease
Publication Type :
Academic Journal
Accession number :
edsdoj.2a0bfa0a93724357a463ac91cd81b295
Document Type :
article
Full Text :
https://doi.org/10.1038/s41419-021-04412-1