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Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.

ABSTRACT: Retinal ischemia followed by reperfusion (IR) is a common cause of many ocular disorders, such as age-related macular degeneration (AMD), which leads to blindness in the elderly population, and proper therapies remain unavailable. Retinal pigment epithelial (RPE) cell death is a hallmark of AMD. Hyperbaric oxygen (HBO) therapy can improve IR tissue survival by inducing ischemic preconditioning responses. We conducted an in vitro study to examine the effects of HBO preconditioning on oxygen-glucose deprivation (OGD)-induced IR-injured RPE cells. RPE cells were treated with HBO (100% O₂ at 3 atmospheres absolute for 90 min) once a day for three consecutive days before retinal IR onset. Compared with normal cells, the IR-injured RPE cells had lower cell viability, lower peroxisome proliferator activator receptor-alpha (PPAR-α) expression, more severe oxidation status, higher blood-retinal barrier disruption and more elevated apoptosis and autophagy rates. HBO preconditioning increased PPAR-α expression, improved cell viability, decreased oxidative stress, blood-retinal barrier disruption and cellular apoptosis and autophagy. A specific PPAR-α antagonist, GW6471, antagonized all the protective effects of HBO preconditioning in IR-injured RPE cells. Combining these observations, HBO therapy can reverse OGD-induced RPE cell injury by activating PPAR-α signalling.

SUBMITTER: Sun TB

PROVIDER: S-EPMC10568664 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.

Sun Tzong-Bor TB Huang Kuo-Feng KF Niu Ko-Chi KC Lin Cheng-Hsien CH Liu Wen-Pin WP Yeh Chao-Hung CH Kuo Shu-Chun SC Chang Ching-Ping CP

Journal of cellular and molecular medicine 20230920 20

Retinal ischemia followed by reperfusion (IR) is a common cause of many ocular disorders, such as age-related macular degeneration (AMD), which leads to blindness in the elderly population, and proper therapies remain unavailable. Retinal pigment epithelial (RPE) cell death is a hallmark of AMD. Hyperbaric oxygen (HBO) therapy can improve IR tissue survival by inducing ischemic preconditioning responses. We conducted an in vitro study to examine the effects of HBO preconditioning on oxygen-gluco ...[more]

PMID: 37731202

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Project description:Dendritic cell (DC) activation induces expression of co-stimulatory surface molecules, as well as migration into secondary lymphoid organs, where they activate naïve T-cells. A family of plant derivatives, eremophilane-type petasite sesquiterpenes, can regulate the immune system through DC targeting due to their anti-inflammatory effects. Peroxisome proliferator-activated receptor gamma (PPARγ) is involved in inhibition of inflammatory responses and induction of DCs to acquire a mucosal phenotype. Since mucosal DCs are central in innate immune responses, we hypothesized that eremophilane-type petasite sesquiterpenes exerted their anti-inflammatory effects by inhibiting DC maturation and activation through PPARγ. This study assessed the bicyclic eremophilane-type petasite sesquiterpene compounds Fukinone and 10βH-8α,12-Epidioxyeremophil-7(11)-en-8β-ol (ZYFDC21 and ZYFDC22) in the maturation and activation of mouse DC. We measured surface expression of co-stimulatory molecules by flow cytometry and cell-free supernatant cytokine production upon lipopolysaccharide stimulation by enzyme-linked immunosorbent assays (ELISAs) in the presence or absence of PPARγ agonists. DCs were generated from C57BL/6 mice bone marrow cells and harvested. Cells were exposed to bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 in the presence or absence of synthetic PPARγ agonists (GW1929 and TGZ) or the natural PPARγ ligand 15d-PGJ2, followed by overnight activation with LPS. We observed differences in the upregulation of surface expression of CD86, along with TNF, IL-6, and IL-12p70 released by DCs stimulated with LPS, when using combinations of bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22, and PPARγ agonists, in particular the PPARγ ligand 15d-PGJ2. Our results indicate that bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 inhibit maturation and activation of DC, and this activity is augmented upon PPARγ activation.

Dataset Information

Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.

Publications

Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.

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