WHY IS THE MACULA PARTICULARLY SUSCEPTIBLE TO NON-EXUDATIVE AGE-RELATED MACULAR DEGENERATION? LESSONS FROM THE MOUSE

HERNÁN H. DIEGUEZ, MARÍA F. GONZÁLEZ FLEITAS, MARCOS L. ARANDA, AGUSTINA IAQUINANDI, FLORENCIA ALTSCHULER, JULIÁN DEVOUASSOUX, MARÍA I. KELLER SARMIENTO, MÓNICA S. CHIANELLI, PABLO H. SANDE, RUTH E. ROSENSTEIN, DAMIÁN DORFMAN; AGUSTINA ALAIMO; HORACIO E. ROMEO

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica

<!-- /* Font Definitions */@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-536870145 1073743103 0 0 415 0;}@font-face{font-family:"MS Mincho";mso-font-alt:"ＭＳ 明朝";mso-font-charset:128;mso-generic-font-family:modern;mso-font-pitch:fixed;mso-font-signature:-536870145 1791491579 18 0 131231 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:Cambria;mso-fareast-font-family:"MS Mincho";mso-bidi-font-family:"Times New Roman";mso-ansi-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-fareast-font-family:"MS Mincho";mso-hansi-font-family:Cambria;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Non-exudativeage-related macular degeneration (NE-AMD) represents the leading cause of blindnessin the elderly. The macular retinal pigment epithelium (RPE) lies in a highoxidative environment because its high metabolic demand, mitochondriaconcentration, reactive oxygen species levels, and macular blood flow. It hasbeen suggested that oxidative stress-induced damage to the RPE plays a key rolein NE-AMD pathogenesis. The fact that the disease limits to the macular regionraises the question as to why this area is particularly susceptible. We havedeveloped a NE-AMD model induced by superior cervical ganglionectomy (SCGx) inC57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribedto the temporal region of the RPE/outer retina. The aim of this work wasanalyzing RPE regional differences that could explain AMD localized susceptibility.Adult male C57Bl/6J mice were used. Histological, ultrastructural andbiochemical parameters were studied. Lower melanin content, thicker basalinfoldings, higher mitochondrial mass, and higher levels of antioxidantenzymes, 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 inthe antioxidant system, and in mitochondria mass, as well as an increase inmitochondria superoxide, lipid peroxidation products, nuclear factor erythroid2?related factor (Nrf2) and heme oxygenase-1 levels, and in the occurrence ofdamaged mitochondria exclusively at the temporal RPE (**P < 0.01 vs. nasalRPE from sham-treated eyes; a: P < 0.01 vs. temporal RPE from sham-treatedeyes, by Tukey´s test (F=4.53)). These findings suggest that despite thewell-known differences between the human and mouse retina, it might not beNE-AMD pathophysiology which conditions the localization of the disease, butthe macular RPE histologic and metabolic specific attributes that make it moresusceptible to choroid alterations leading initially to a localized RPEdysfunction/damage, and secondarily to macular degeneration.