Abstract
Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved. Our results revealed that GlcN had no effect on phagocytosis of POS at the lower doses. GlcN treatment induced autophagy in cells. GlcN decreased the LLAF in native POS-treated cells, whereas malondialdehyde or 4-hydroxynonenal-modified POS attenuated this effect. 3-Methyladenine inhibited GlcN-induced autophagy and attenuated the effect of GlcN on the decrease of the native POS-derived LLAF. Furthermore, GlcN induced the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR), whereas Compound C inhibited these effects of GlcN. Altogether, these results suggest that GlcN decreased the native POS-derived LLAF through induction of autophagy, at least in part, by the AMPK–mTOR pathway. This mechanism has potential for the preventive treatment of lipofuscin-related retinal degeneration such as AMD.
Highlights
Age-related macular degeneration (AMD) is a progressive deterioration of the macula of the retina associated with aging
We previously reported the role of GlcN in the inhibition of inflammatory reactions induced by inflammatory cytokines in human retinal pigment epithelial (RPE) cells; its anti-inflammatory effect in a rat model of endotoxin-induced uveitis [25,26,27]; suppression of epithelial-to-mesenchymal transformation of RPE cells, both in vivo and in vitro [28]; and protection of retinal ganglion cells from oxidative stress injury in a rat model of ischemia–reperfusion injury [29]
Given that autophagy can be induced by GlcN in many cell types, we further investigated whether GlcN could induce the activation of autophagy in ARPE-19 cells
Summary
Age-related macular degeneration (AMD) is a progressive deterioration of the macula of the retina associated with aging. AMD is the chief cause of irreversible vision loss among people aged 50 years and older in the developed world [1]. The wet form affects approximately 10–15% of all patients with AMD and accounts for 90% of all cases of vision loss associated with the disease [3]. The dry form is more common and affects 85–90% of all patients with AMD. Stage of dry AMD is associated with mild vision loss and the presence of drusen in the macula [4]. Later, it progresses to GA, causing irreversible vision loss [5]. It is important to develop preventive strategies in dry AMD through nutrient supplementation
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