Decorin Protects Retinal Pigment Epithelium Cells from Oxidative Stress and Apoptosis via AMPK-mTOR-Regulated Autophagy

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss among the elderly worldwide with unidentified pathogenesis and limited therapeutic options. Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is central in the development and progression of AMD. Decorin (DCN), a small leucine-rich proteoglycan, possesses powerful antifibrotic, anti-inflammatory, and antiangiogenic properties. DCN has also been reported to serve a cytoprotective role in various cell types, but its protective effects against H2O2-induced oxidative stress and apoptosis in ARPE-19 cells remain unclear. In this study, we showed that DCN significantly attenuated the increase in cell viability loss, apoptosis rate, and reactive oxygen species (ROS) levels in ARPE-19 cells induced by H2O2. Furthermore, DCN activated the AMPK/mTOR pathway to promote autophagy while genetic inhibition of autophagy-related gene 5 (ATG5) hindered autophagic process and diminished the protective role of DCN against oxidative stress in ARPE-19 cells. Collectively, these results suggest that DCN could protect RPE cells from H2O2-induced oxidative stress and apoptosis via autophagy promotion, thus providing the therapeutic potential for AMD prevention and treatment.

Calpain-2 Facilitates Autophagic/Lysosomal Defects and Apoptosis in ARPE-19 Cells and Rats Induced by Exosomes from RPE Cells under NaIO3 Stimulation

“…It is well known that abnormal autophagy and apoptosis contribute to the development of AMD [ 38 , 39 ]. Our data showed that the dying cells displayed a large-scale accumulation of autophagosomes following NaIO 3 insult.…”

Phloroglucinol Attenuates DNA Damage and Apoptosis Induced by Oxidative Stress in Human Retinal Pigment Epithelium ARPE-19 Cells by Blocking the Production of Mitochondrial ROS

“…In this respect, pharmacological manipulation of autophagic activity could be a therapeutic target for retinal damage-related disorders. Although autophagy in RPE cells exposed to oxidative stress, particularly H 2 O 2 , is known to contribute to apoptosis induction [ 49 ], RPE cells might also be protected from oxidative stress and apoptosis through promotion of autophagy [ 59 ]. In this study, H 2 O 2 -induced autophagy in ARPE-19 cells was blocked by 3-MA, an autophagosome blocker, suggesting that H 2 O 2 -mediated autophagy might contribute to apoptosis induction.…”

Global impact of proteoglycan science on human diseases

“… 227 The beneficiary effect on “cellular protection” is also shown by the finding that decorin protects intestinal cells via its pro-autophagic action in inflammatory bowel disease 228 and seemingly protects retinal pigment epithelial cells from oxidative stress and apoptosis via AMPK-mTOR-regulated autophagy. 229 Moreover, decorin evokes reversible mitochondrial depolarization in carcinoma and vascular endothelial cells. 230 This pathway is novel and requires further elucidation; decorin-evoked mitophagy requires TCHP/mitostatin mRNA interaction with PGC-1α which results in accumulation of mitostatin.…”