Lipid Droplet Accumulation Promotes RPE Dysfunction

Abstract

Non-exudative age-related macular degeneration (AMD) is an irreversibly progressive retinal degenerative disease characterized by dysfunction and loss of retinal pigment epithelium (RPE). It has been suggested that impaired phagocytosis of the RPE is involved in the progression of non-exudative AMD, but the mechanism is not fully clear. In this study, we investigated the effect of lipid droplet accumulation on RPE function. Compared to young mice, the expression of lipid droplet-associated proteins increased in the RPE-choroidal complex, and lipid droplet in the RPE was observed in aged pigmented mice (12-month-old). Repeated treatment of the photoreceptor outer segment against ARPE-19 resulted in lipid droplets in ARPE-19 cells in vitro. Oleic acid treatment for ARPE-19 cells to form intracellular lipid droplet reduced the POS uptake into the ARPE-19 cells without causing a decrease in cell viability. The suppression of the POS uptake by lipid droplet formation improved by inhibiting lipid droplet formation using triacsin C. Moreover, the amount of intracellular reactive oxygen species was suppressed by the triacsin C treatment. These results indicate that lipid droplet is involved in the RPE dysfunction, and inhibiting lipid droplet formation may be a target for preventing and treating non-exudative AMD.

Extracellular vesicles from organoid‐derived human retinal progenitor cells prevent lipid overload‐induced retinal pigment epithelium injury by regulating fatty acid metabolism

“…Among various lipid components, fatty acids, especially oleic acid, are present in the subretinal space and recognised as critical risk factors for AMD (Agrón et al, 2021). Consistently, an overload of oleic acid causes lipid deposition, dysfunction and a decline in RPE cell viability (Yako et al, 2022). Thus, recovering the function of lipid metabolism in RPE cells and clearing lipids deposited in the subretinal space are potential treatments for AMD (Landowski & Bowes Rickman, 2021;Ren et al, 2022).…”

Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina

“… 45 Another interesting observation is that RPE cells contain organelles named retinosomes, which are retinyl ester-containing lipid droplets important to keep a proper supply of the visual chromophore 11-cis-retinal to the photoreceptor cells. 46 Changes in the formation of these lipid droplets (retinosomes) have been associated with pathological conditions in the retina of drosophila and rat, 47 , 48 in addition to patients suffering from age-related macular degeneration (AMD). 49 Although in our lipidomic analysis we did not look specifically at retinyl esters, it is noteworthy the increase in expression of lecithin-retinol acyltransferase ( Lrat ), which encodes the enzyme responsible for the esterification of trans -retinal, producing trans -retinyl esters.…”

Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations

“…Furthermore, the interaction between RPE, Müller glia, and neuronal cells in retina is also important for the modulation of lipid availability and clearance of neighboring photoreceptors (Fu et al, 2021). For example, disrupted lipid homeostasis in RPE causes lipid droplet formation and RPE dysfunction with aging (Yako et al, 2022). Interestingly, peroxisomes and lipid droplets have physical interaction within cells.…”