Abstract
Purpose :
Non-exudative age-related macular degeneration (NE-AMD), the main cause of blindness in the elderly, is characterized by the progressive atrophy of photoreceptors and retinal pigment epithelium (RPE) exclusively localized at the macular region (without affecting the extramacular retina) even at advanced stages. The fact that NE-AMD limits to the macular region raises the question as to why this area is particularly susceptible. Although it was classically assumed that mice do not have a macula, it has been shown that the temporal region (respect to the optic nerve) of the outer retina from C57BL/6J mice shares some similarities with the human macula. The macula lies in a high oxidative environment because of the high macular blood flow and metabolic demand that generates oxidant species. Probably due to this, the RPE is enriched in mitochondria, which are a major source of oxidant species. Our aim was analysing the temporal (i.e., macular-like) versus the nasal (i.e., non-macular) outer retina structural and metabolic characteristics that could underlie the NE-AMD-induced damage circumscribed to the temporal retina.
Methods :
RPE melanin content (histology), RPE ultrastructure (electron microscopy), mitochondria mass (MitoTracker-Red, Western blot and electron microscopy) and antioxidant system status (immunohistochemistry and Western blot) were assessed at the temporal and nasal region of the retina and RPE from adult male C57BL/6J mice.
Results :
RPE melanin content and melanosome number were lower at the temporal region (n=5 P<0.01 by t-test), whereas temporal RPE basal infoldings were thicker compared to the nasal region (n=5 P<0.01). Viable mitochondria number and specific mitochondrial protein levels were higher at the temporal RPE (n=5 P<0.01). RPE catalase, superoxide dismutase 1 and 2, and glutathione peroxidase levels were higher at the temporal RPE (n=5 P<0.01). None of these parameters differed between the temporal and nasal regions of the neural retina.
Conclusions :
Macular RPE oxidative stress and mitochondrial damage are key players in NE-AMD. The highest antioxidant defence system and mitochondria mass at the temporal region could underlie its susceptibility to the circumscribed NE-AMD damage, supporting that the specific localization of the disease could be conditioned by histologic and metabolic RPE specific regional attributes.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.