Lipofuscin-mediated photodynamic stress induces adverse changes in nanomechanical properties of retinal pigment epithelium cells

Abstract

Retinal pigment epithelium (RPE) is an important part of the blood-retina barrier (BRB) that separates the retina from the choroid. Although melanin granules contribute to the mechanical stability of the BRB complex, it is unknown if the age pigment lipofuscin affects mechanical properties of the tissue. To address this issue the effect of sub-lethal photic stress mediated by phagocytized lipofuscin granules, isolated from RPE of human donors, on morphology and mechanical properties of ARPE-19 cells was investigated. Nanomechanical analysis using atomic force spectroscopy revealed that irradiation of cells containing lipofuscin granules with blue light induced significant softening of the cells, which was accompanied by substantial reorganization of the cell cytoskeleton due to peroxidation of cellular proteins. Our results indicate that lipofuscin-mediated photic stress can cause significant modification of the RPE cells with the potential to disturb biological function of the BRB complex.

Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

“…Regarding the latter point, oxidative stress represents one of the major lethal mechanisms responsible for age-related RPE damages [39]. Many studies have demonstrated that accumulation of lipid deposit called lipofuscin generates reactive oxygen species through phototoxicity in RPE cells [40][41][42]. Oxidative stress triggered by photo-oxidation of bis-retinoid A2E, a lipofuscin constituent, is well known to be a progression factor of age-related macular degeneration and also in genetic macular degeneration syndromes such as Stargardt disease [43], but very little is known about A2E involvement in retinitis pigmentosa.…”

Photoreactivity of Bis-retinoid A2E Complexed with a Model Protein in Selected Model Systems

“…Although chronic oxidative stress may disturb many biological functions of RPE/photoreceptor complex, the key molecular targets that are subjected to oxidative modifications remain mostly unknown. We consider changes in the cytoskeleton of human RPE cells as one of the most sensitive indicators of oxidative modifications, which accompany chronic phototoxicity [29,57]. Future research should focus on identification of the cytoskeletal proteins that might be oxidatively modified under chronic oxidative stress conditions, leading to disruption of key functions of the RPE/ photoreceptor complex.…”

“…We believe that oxidative modifications of cytoskeletal proteins may have adverse effect on both morphology and nanomechanical properties of RPE cells [27,28]. Recently, Wiktor et al [29]. have demonstrated that sublethal or weakly lethal photic stress, mediated by human RPE lipofuscin granules, affected nanomechanical properties of ARPE-19 cells.…”

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

“…50 cells for each condition were analyzed. Detailed description of the mechanical analysis used in this work can be found elsewhere 41 . To examine the effect of melanin on the nanomechanical properties of melanoma cells at the cellular level, probes with spheres attached to the end of the cantilevers were chosen.…”