Why is the macula particularly susceptible to dry age-related macular degeneration? Lessons from mice

DIEGUEZ, HERNÁN H.; GONZÁLEZ FLEITAS, MARÍA FLORENCIA; DORFMAN, DAMIÁN; ALAIMO, AGUSTINA; ROSENSTEIN, RUTH E.; ROMEO, HORACIO E.; ARANDA, MARCOS L.

Córdoba

Congreso; XXXIII Congreso Anual SAN 2018; 2018

SAN

Dry age -related macular degeneration (dAMD), the elderly main cause of blindness,  is characterized by retinal pigment epithelium (RPE) and photoreceptors atrophy circumscribed to    the macula. The fact that only the macula is damaged by dAMD, raises question as to why ct that , , raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD, raises question as to why ct that only the macula is damaged by dAMD,  raises question as to why this area particularly susceptible. It has been suggested that RPE oxidative damage plays an important role in dAMD pathogenesis. However, the exact mechanisms of disease are elusive and hard to study, as mice do not have a macula. We developed dAMD model  induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. In this context, the aim of this work was analyzing RPE regional differences that could explain dAMD could explain dAMD localized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with enzymes, were found in the temporal RPE compared with the nasal region. Moreover, SCGx induced a decrease in antioxidant system, and mitochondria mass, as well an increase in mitochondria superoxide, lipid peroxidation products,  nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria 1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE. These findings suggest it might not be dAMD pathophysiology but the macular RPE histologic and metabolic specific attributes which conditions the localization of the disease.