WHY IS THE MACULA PARTICULARLY SUSCEPTIBLE TO DRY AGE-RELATED MACULAR DEGENERATION? LESSONS FROM MICE

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

Córdoba

Congreso; XXXIII Congreso Anual SAN; 2018

Sociedad Argentina de Investigación en Neurociencias

P274.-WHY IS THE MACULA PARTICULARLY SUSCEPTIBLE TO DRY AGE-RELATEDMACULAR DEGENERATION? LESSONS FROM MICEHernán H Dieguez1 ,Horacio E. Romeo2, Agustina Alaímo3, María F. González Fleitas1, Marcos L. Aranda1, Ruth E. Rosenstein1, Damian Dorfman11 Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquimica Humana.Fac. de Medicina/CEFyBo; UBA/CONICET, 2 Fac. de Ingeniería y Cs. Agrarias.- BIOMED/UCA/CONICET, 3 Laboratorio Interdisciplinario de Dinámica Celular y Nanoherramientas, Departamento de Química Biológica. Fac. Cs Exactas y Naturales/IQUIBICEN; UBA/CONICETPresenting author: Hernán Dieguez, her.die.14@gmail.com_________________________________________________________________________________________Dry age-related macular degeneration (dAMD), the elderly main cause of blindness, ischaracterized by retinal pigment epithelium (RPE) and photoreceptors atrophy circumscribed tothe macula. The fact that only the macula is damaged by dAMD, raises the question as to why isthis area particularly susceptible. It has been suggested that RPE oxidative damage plays animportant role in dAMD pathogenesis. However, the exact mechanisms of the disease are stillelusive and hard to study, as mice do not have a macula. We have developed a dAMD modelinduced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces thedisease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. In thiscontext, the aim of this work was analyzing RPE regional differences that could explain dAMDlocalized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrialmass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared withthe nasal region. Moreover, SCGx induced a decrease in the antioxidant system, and inmitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products,nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondriaexclusively at the temporal RPE. These findings suggest it might not be dAMD pathophysiology butthe macular RPE histologic and metabolic specific attributes which conditions the localization ofthe disease.