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Palmitic Acid Induced a Long-Lasting Lipotoxic Insult in Human Retinal Pigment Epithelial Cells, which Is Partially Counteracted by TRAIL. | LitMetric

AI Article Synopsis

  • Hyperglycaemia and saturated fatty acids like palmitic acid (PA) contribute to the development of diabetic retinopathy in type 2 diabetes mellitus (T2DM) through increased cell apoptosis and oxidative stress.
  • This study assessed TRAIL's potential to mitigate PA-induced damage in retinal pigment epithelial cells (ARPE-19), finding that TRAIL largely failed to prevent cell death when applied simultaneously with PA but had some protective effects when administered afterward.
  • The findings suggest that TRAIL may help reduce inflammation and oxidative stress in retinal cells, but more research is needed to determine its therapeutic value for treating diabetic retinopathy.

Article Abstract

Hyperglycaemia and increased circulating saturated fatty acids are key metabolic features of type 2 diabetes mellitus (T2DM) that contribute to diabetic retinopathy pathogenesis. Contrarily, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been shown to improve or prevent T2DM. This study aimed at investigating the effect of TRAIL in an in vitro model of human retinal pigment epithelium: the ARPE-19 cell line, treated with palmitic acid (PA) in the presence of high glucose concentration. PA caused a drop in cellular metabolic activity and cell viability as well as an increase in apoptosis rates, which were paralleled by an upregulation of reactive oxygen species (ROS) generation as well as mitochondrial fragmentation. Despite ARPE-19 cells expressing TRAIL-R2 at the cell surface, TRAIL failed to counteract the cytotoxic effects of PA. However, when TRAIL was used alongside PA and then removed or used alone following PA challenge, it partially attenuated PA-induced lipotoxicity. This effect of TRAIL appeared to rely upon the modulation of inflammation and ROS production. Thus, TRAIL exerted a trophic effect on ARPE-19 cells, which became evident only when the lipotoxic insult was removed. Nevertheless, whether recombinant TRAIL might have a therapeutic potential for the treatment of diabetic retinopathy requires further investigation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774631PMC
http://dx.doi.org/10.3390/antiox11122340DOI Listing

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