Non-Exudative Age-Related Macular Degeneration: New Experimental Insights

Non-exudativeage-related macular degeneration (NE-AMD), the main cause of blindness in theelderly, is a condition involving progressive atrophy of the retinal pigment epitheliumand photoreceptors exclusively localized at the central retina (i.e., themacula). Clinically, NE-AMD appears as a progressive defect in central vision,leading to legal blindness. NE-AMD is a multi-factorial disease; retinalpigmentary epithelium lipofuscin accumulation, choroidal blood flowinsufficiency, inflammation, and oxidative stress have been involved in thedisease etiopathogenesis. The observation that the disease is circumscribed tothe macular area, raises the question as to why the macula is particularlysusceptible to the disease, while the rest of the retina remains (at leastclinically) unaltered. Although there are no definitive answers to thisquestion, the explanation is likely to be related to both the metabolic andstructural attributes of this particular retinal region that differ from itssurroundings, and to the alterations induced by the disease itself. Over thelast decade, there have been an increasing number of reports describing rodent[R1] models (mostly in mice), which mimic somecharacteristics compatible with human NE-AMD. However, most of them are notable to reproduce the hallmarks of the disease (i.e., its specificlocalization), which added to the lack of a macula in rodents, has made thestudy of NE-AMD particularly difficult. Although impairment of choroidal bloodflow is one of the supposed pathogenic mechanisms, there were no experimentalmodels addressing this risk factor. In this chapter, we will discuss: 1) the recentdevelopment of a new experimental model of NE-AMD induced by superior cervicalganglionectomy in C57BL/6J mice, 2) differences in the histology,ultrastructure, and metabolic attributes of the temporal (versus the nasal) retinalpigment epithelium, which could explain its particular susceptibility withinNE-AMD, and 3) the participation of retinal pigment epithelium oxidative damageand mitochondrial alterations in the pathogenic mechanisms of experimentalNE-AMD.Fil: Dieguez, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Dorfman, Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin