Aging is not a disease: Distinguishing age-related macular degeneration from aging

Abstract

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

“…The integrity of the RPE cell monolayer is essential for normal functioning of the visual system, and indeed, a prominent feature of pathological aging in the retina is the development of areas of RPE atrophy, not only in AMD (Ardeljan & Chan, 2013; Mullins et al ., 2014; Ozaki et al ., 2014), but also in many forms of inherited retinal degeneration (McBain et al ., 2012). Indeed, ‘dry’ AMD (geographic atrophy) is considered a form of apoptotic and/or necrotic cell death, possibly related to the loss of complement regulatory proteins (Ebrahimi et al ., 2013; Hanus et al ., 2013).…”

Effect of aging and lifestyle on photoreceptors and retinal pigment epithelium: cross-sectional study in a healthy Danish population

“…Large multinucleated RPE cells have an increased metabolic demand, which as a consequence increases the reactive oxygen species generated. Exposure to reactive oxygen species may affect the health of photoreceptors and the Bruch’s membrane [24]. RPE isolated from young and old rats share only ~50% of their protein expression and the differences concern mostly proteins involved in pathways of oxidative stress such as catalase, glutathione peroxidase, and superoxidate dismutase [25].…”

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

“…A year later Heinrich Müller coined the name drusen, after their glistening appearance, from the German word for geode, a rock containing a crystal lined cavity (Muller, 1856). Drusen may be a manifestation of the normal ageing process or represent an important sign associated with retinal disease (Ardeljan and Chan, 2013). Differentiating the two depends upon a careful assessment of the drusen characteristics, although there is a degree of overlap.…”