Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative Age-related Macular Degeneration

ALAIMO A.; ROSENSTEIN RE; ROMEO EH; ARANDA ML; DIEGUEZ HH; GONZÁLEZ FLEITAS MF; DORFMAN D; ROMEO EH; ALAIMO A.; ARANDA ML; ROSENSTEIN RE; DIEGUEZ HH; GONZÁLEZ FLEITAS MF; DORFMAN D

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2019 vol. 131 p. 72 - 80

0891-5849

Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause ofblindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidativeenvironment because its high metabolic demand, mitochondria concentration, reactive oxygenspecies levels, and macular blood flow. It has been suggested that oxidative stress-induceddamage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits tothe macular region raises the question as to why this area is particularly susceptible. We havedeveloped a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6Jmice, which reproduces the disease hallmarks exclusively circumscribed to the temporal regionof the RPE/outer retina. The aim of this work was analyzing RPE regional differences that couldexplain AMD localized susceptibility. Lower melanin content, thicker basal infoldings, highermitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPEcompared with the nasal region. Moreover, SCGx induced a decrease in the antioxidant system,and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidationproducts, nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damagedmitochondria exclusively at the temporal RPE. These findings suggest that despite the wellknowndifferences between the human and mouse retina, it might not be NE-AMDpathophysiology which conditions the localization of the disease, but the macular RPE histologicand metabolic specific attributes that make it more susceptible to choroid alterations leadinginitially to a localized RPE dysfunction/damage, and secondarily to macular degeneration.