Exposure to enriched environment protects the central retinal pigment epithelium and retina on a dry-AMD experimental model in mice

ALAIMO A; ROSENSTEIN RE; DIEGUEZ HH; GONZALEZ FLEITAS MC; DORFMAN D; ROMEO EH; CALANNI JS

San Francisco

Congreso; ARVO Annual Meeting; 2021

ASSOCIATION FOR RESEARCH IN VISION AND OPHTHALMOLOGY

Purpose : Dry age-related macular degeneration (dAMD), the main blindness cause in the elderly, is characterized by retinal pigment epithelium (RPE) and photoreceptors (PR) atrophy circumscribed to the macular area. At the moment, there are no effective therapies to prevent or delay the vision loss affecting dAMD patients. We have developed a dAMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the RPE/outer retina temporal region. Environmental enrichment (EE) is a complex condition that boosts physical and social stimulation. Several reports show that EE provides a better recovery from different neuropathology and retinal alterations. In this context, our aim was analyzing the effect of EE on the alterations induced by experimental dAMD.Methods : Adult male C57BL/6j mice were submitted to unilateral SCGx, were as the contralateral side was submitted to a sham procedure. Animals were continuously exposed to SE or EE during different intervals. Visual function (electroretinography and visual behavior tests) was analized at 4, 6 and 10 weeks post-SCGx. Retinal histology and ultrastructure were analyzed at 10 weeks post-SCGx. RPE mitocondria and oxidative stress markers were assessed by Western blotting, specific probes, and immunofluorescence at 6 weeks post-SCGx.Results : SCGx induced a reduction of the melanin content and RPE65 inmunoreactivity at the temporal RPE, as well as a decrease in mitochondria mass, an increase in mitochondria superoxide and lipid peroxidation products. Moreover, SCGx induced ultrastructural alterations at the temporal RPE and PR. EE did not prevent SCGx-induced choroid alterations but significantly prevented the visual dysfunction, histology and ultrastructure alterations, mitochondria and oxidative stress. Moreover, EE reversed the functional and structural damage induced by SCGx when started at 4 weeks post-surgery.Conclusions : Therefore, exposure to EE prevented, and reversed the damage induced by experimental dAMD, probably through RPE mitochondria protection and RPE oxidative damage prevention, thus becoming as a promising novel therapeutic strategy for dAMD.