Role of Mitochondria in Retinal Pigment Epithelial Aging and Degeneration

Tong, Yao; Zhang, Zunyi; Wang, Shusheng

doi:10.3389/fragi.2022.926627

Cited by 37 publications

(34 citation statements)

References 236 publications

(244 reference statements)

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“…In healthy retinal cells, ROS levels remain low as a result of normal cellular metabolism. However, accumulation of ROS caused by oxidative stress can act as an initiator in the pathogenesis of degenerative diseases of the retina [ 4 , 35 ]. In this study, inhibition of cell survival, induction of cytotoxicity, and generation of ROS by H 2 O 2 in ARPE-19 cells were significantly suppressed by pretreatment with phloroglucinol or NAC, a free-radical scavenger used as a positive control.…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2022

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Phloroglucinol, a phenolic compound, is known to possess a potent antioxidant ability. However, its role in retinal cells susceptible to oxidative stress has not been well elucidated yet. Thus, the objective of this study was to evaluate whether phloroglucinol could protect against oxidative damage in cultured human retinal pigment epithelium ARPE-19 cells. For this purpose, ARPE-19 cells were stimula ted with hydrogen peroxide (H2O2) to mimic oxidative stress. Cell viability, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial function, DNA damage, and autophagy were then assessed. Our results revealed that phloroglucinol ameliorated cell viability, cytotoxicity, and DNA damage in H2O2-exposued ARPE-19 cells and blocked production of ROS. Phloroglucinol also counteracted H2O2-induced apoptosis by reducing Bax/Bcl-2 ratio, blocking activation of caspase-3, and inhibiting degradation of poly (ADP-ribose) polymerase. H2O2 caused mitochondrial impairment and increased expression levels of mitophagy markers such as PINK1and PARKIN known to be associated with mitochondrial ROS (mtROS) generation and cytosolic release of cytochrome c. However, these changes were significantly attenuated by phloroglucinol. Mito-TEMPO, a selective mitochondrial antioxidant, further enhanced the protective effect of phloroglucinol against dysfunctional mitochondria. Furthermore, H2O2 induced autophagy, but not when ARPE-19 cells were pretreated with phloroglucinol, meaning that autophagy by H2O2 contributed to the pro-survival mechanism and that phloroglucinol protected ARPE-19 cells from apoptosis by blocking autophagy. Taken together, these results suggest that phloroglucinol can inhibit oxidative stress-induced ARPE-19 cell damage and dysfunction by protecting DNA damage, autophagy, and subsequent apoptosis through mitigation of mtROS generation. Thus, phloroglucinol might have therapeutic potential to prevent oxidative stress-mediated damage in RPE cells.

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Section: Discussionmentioning

confidence: 99%

“…These results showed the possibility that phloroglucinol could block ROS generation caused by oxidative stress. Many previous studies have shown that DNA damage and apoptosis can be induced in RPE cells exposed to oxidative stimuli [ 35 , 36 ]. This finding was also confirmed in H 2 O 2 -treated ARPE-19 cells.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…The retinal absorption of ultraviolet rays causes photochemical damage to mitochondria in the RPE, leading to increased ROS generation [ 235 , 236 ]. Specifically, blue light has been associated with significant photooxidative stress and ROS generation [ 237 , 238 ].…”

Section: Retinamentioning

confidence: 99%

Role of Oxidative Stress in Ocular Diseases: A Balancing Act

et al. 2023

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Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative stress and mitochondrial dysfunction in conditions affecting both the anterior segment (e.g., dry eye disease, keratoconus, cataract) and posterior segment (age-related macular degeneration, proliferative vitreoretinopathy, diabetic retinopathy, glaucoma) of the human eye. We posit that further development of therapeutic interventions to promote pro-regenerative responses and maintenance of the redox balance may delay or prevent the progression of these major ocular pathologies. Continued efforts in this field will not only yield a better understanding of the molecular mechanisms underlying the pathogenesis of ocular diseases but also enable the identification of novel druggable redox targets and antioxidant therapies.

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“…Dysfunction of mitochondria is a signal indicating cellular senescence, and mitochondrial injury finally results in RPE cell death and degenerative retinal disease [ 90 ]. Both aging and hyperglycemia can lead to oxidative stress, damaging mitochondria and accelerating AMD and RD development [ 91 ]. In glaucoma, mitochondrial dysfunction is accompanied with retinal ganglion cell (RGC) degeneration [ 92 ], which is difficult to repair.…”

Section: Strategies For Treating the Retinal Diseases With Mesenchyma...mentioning

confidence: 99%

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases

Chen

Jiang

Duan

et al. 2022

Genes

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Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions.

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Role of Mitochondria in Retinal Pigment Epithelial Aging and Degeneration

Cited by 37 publications

References 236 publications

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

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

Role of Oxidative Stress in Ocular Diseases: A Balancing Act

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases

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