Why is the macula particularly susceptible to non-exudative age-related macular degeneration? Lessons from the mouse

DIEGUEZ HH; ROMEO EH; ALAIMO A; GONZÁLEZ FLEITAS MF; ARANDA ML; IAQUINANDI A; ALTSCHULER F; DEVOUASSOUX J; KELLER IS; CHIANELLI M; SANDE PH; ROSENSTEIN RE; DORFMAN D

Mar del Plata

Congreso; LXIII Reunion Cientifica Anual Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Non-exudative age-related macular degeneration (NEAMD) represents the leading cause of blindness in theelderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its highmetabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It hasbeen suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible. We have developed a NE-AMD 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. The aim of this work was analyzing RPE regional differences that could explain AMD localized susceptibility. Adult male C57Bl/6J mice were used. Histological, ultrastructural and biochemical parameters were studied. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with the nasal region (*P < 0.05 vs. nasal RPE, by Student´s t-test). Moreover, SCGx induced a decrease in the antioxidant system, and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products, nuclear factor erythroid 2?related factor (Nrf2) and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE (**P < 0.01 vs. nasal RPE from sham-treated eyes; a: P < 0.01 vs. temporal RPE from sham-treated eyes, by Tukey´s test (F=4.53)). These findings suggest that despite the well-known differences between the human and mouse retina, it might not be NE-AMD pathophysiology which conditions the localization of the disease, but the macular RPE histologic and metabolic specific attributes that make it more susceptible to choroid alterations leading initially to a localized RPE dysfunction/damage, and secondarily to macular degeneration.