Urban Aerosol Particulate Matter Promotes Necrosis and Autophagy via Reactive Oxygen Species-Mediated Cellular Disorders that Are Accompanied by Cell Cycle Arrest in Retinal Pigment Epithelial Cells

Abstract

Urban particulate matter (UPM) is recognized as a grave public health problem worldwide. Although a few studies have linked UPM to ocular surface diseases, few studies have reported on retinal dysfunction. Thus, the aim of the present study was to evaluate the influence of UPM on the retina and identify the main mechanism of UPM toxicity. In this study, we found that UPM significantly induced cytotoxicity with morphological changes in ARPE-19 human retinal pigment epithelial (RPE) cells and increased necrosis and autophagy but not apoptosis. Furthermore, UPM significantly increased G2/M arrest and simultaneously induced alterations in cell cycle regulators. In addition, DNA damage and mitochondrial dysfunction were remarkably enhanced by UPM. However, the pretreatment with the potent reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) effectively suppressed UPM-mediated cytotoxicity, necrosis, autophagy, and cell cycle arrest. Moreover, NAC markedly restored UPM-induced DNA damage and mitochondrial dysfunction. Meanwhile, UPM increased the expression of mitophagy-regulated proteins, but NAC had no effect on mitophagy. Taken together, although further studies are needed to identify the role of mitophagy in UPM-induced RPE injury, the present study provides the first evidence that ROS-mediated cellular damage through necrosis and autophagy is one of the mechanisms of UPM-induced retinal disorders.

The Protective Effect of Topical Spermidine on Dry Eye Disease with Retinal Damage Induced by Diesel Particulate Matter2.5

“…Furthermore, Chua et al [ 57 ] reported that subjects exposed to higher levels of PM 2.5 were associated with changes in retinal structure features, including RCG and IPL thickness. Previously, we suggested that PM 2.5 mediates retinal dysfunction through ROS-mediated epithelial-mesenchymal transition and necrotic and autophagic cell death in retinal pigment epithelial cells [ 64 , 65 ]. Additionally, our current findings showed that topical exposure to PM 2.5 led to the loss of retinal ganglion cells and the decrease of the NFL/GCL+IPL thickness; however, spermidine eye drops contribute to the normalization of retinal ganglion cell density and retinal structure.…”

The Protective Effect of Oral Application of Corni Fructus on the Disorders of the Cornea, Conjunctiva, Lacrimal Gland and Retina by Topical Particulate Matter 2.5

“…Furthermore, a correlation between PM 2.5 and changes in retinal structure features in subjects exposed to higher levels of PM 2.5 was reported [ 59 ]. Previously, we suggested that PM 2.5 mediates retinal dysfunction through ROS-mediated epithelial–mesenchymal transition and necrotic and autophagic cell death in retinal pigment epithelial cells [ 62 , 63 ]. Our present findings showed that topical exposure to PM 2.5 led to the loss of retinal ganglion cells and the decrease of the NFL/GCL + IPL thickness; however, oral administration of CFW contributed to the normalization of retinal ganglion cell density and retinal constitution.…”

Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

“…After the indicated treatment, the cells were fixed with 4% paraformaldehyde, permeabilized in 0.5% Triton X-100 and then blocked with 2% bovine serum albumin (Sigma-Aldrich Chemical Co.) as described previously ( Lee et al, 2021 ). Subsequently, the cells were probed with anti-p-Nrf2 antibody (Ser 139) at 4°C overnight and then washes with ice-cold PBS.…”