Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice

Abstract

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease, characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Despite there are experimental murine models, the vast majority take too long to develop retinal alterations, which in general are ubiquitous, many result from non-eye specific genetic manipulations, and most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which together with the parasympathetic system, regulate the blood flow. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy on the choroid, Bruch's membrane, retinal pigment epithelium, and retina. Adult male C57BL/6J mice were submitted to unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, retinal pigment epithelium melanin content and retinoid isomerohydrolase loss, drusen-like deposit occurrence, and retinal pigment epithelium and photoreceptors atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptors apoptosis, and photoreceptors electroretinographic function decline. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies.