Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas

Yao, Fei; Zhang, Xuan; Yao, Xueyan; Ren, Xiaohua; Xia, Xiaobo; Jiang, Jian; Ding, Lexi

doi:10.3389/fmed.2021.788663

Cited by 6 publications

(5 citation statements)

References 51 publications

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“…Retinal ischemia–reperfusion down‐regulated PPAR‐α expression in vitro and in vivo 4,15 . Fenofibric acid (a PPAR‐α agonist) treatment promoted survival of ischemic retinal cells via enhancing the expression of endogenous PPAR‐α and promoting survival of retinal ganglion cells and mitigating thinning of the ganglion cell complex 8 . Overexpression of PPAR‐α ameliorated both retinal inflammation and retinal vascular leakage via alleviating retinal neovascularization in diabetic retinopathy 4,16 .…”

Section: Discussionmentioning

confidence: 99%

“… 4 , 15 Fenofibric acid (a PPAR‐α agonist) treatment promoted survival of ischemic retinal cells via enhancing the expression of endogenous PPAR‐α and promoting survival of retinal ganglion cells and mitigating thinning of the ganglion cell complex. 8 Overexpression of PPAR‐α ameliorated both retinal inflammation and retinal vascular leakage via alleviating retinal neovascularization in diabetic retinopathy. 4 , 16 Fenofibrate therapy also alleviated retinopathy by reducing retinal inflammation and oxidative stress in both the ischemic retina 7 and age‐related macular degeneration.…”

Section: Discussionmentioning

confidence: 99%

“… 4 , 5 A previous study demonstrated that PPARα, but not PPARβ or PPARγ, is down‐regulated in diabetic retinopathy. 4 Fenofibrate (a PPAR‐α agonist) alleviates apoptosis of capillary pericytes 6 , 7 or loss of retinal ganglion cells 8 in the ischemic retina. This raises the possibility that PPAR‐α is significantly down‐regulated during IR injury to RPE cells.…”

Section: Introductionmentioning

confidence: 99%

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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,

Huang,

Niu

et al. 2023

J Cellular Molecular Medi

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Sun,

Huang,

Niu

et al. 2023

J Cellular Molecular Medi

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“…I t is generally accepted that ischaemia-reperfusion (I/R)induced tissue damage is not only related to the degree of reduced blood flow, but also to intracellular calcium overload, oxidative stress, inflammatory responses, neurotoxicity of excitatory amino acids, excessive nitric oxide synthesis, and disturbances in energy metabolism [1] , ultimately causing tissue damage and neuronal cell necrosis/apoptosis with the process causing an increase in reactive oxygen species (ROS), including superoxide (O 2-), hydrogen peroxide (H 2 O 2 ) and hydroxyl radicals, leading to DNA fracture, lipid peroxidation and protein inactivation [2][3] . The mechanisms by which I/R injury to tissue occurs are complex and include primary injury in the early stages of ischaemia and secondary injury following reperfusion [4] , which is further exacerbated by I/R caused by the restoration of tissue blood supply after ischaemia has occurred. It is a common cause of visual impairment and blindness in all forms Int J Ophthalmol, Vol.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

Zhou¹,

Xie²,

Zhou³

et al. 2023

Int J Ophthalmol

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AIM: To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. METHODS: The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. RESULTS: Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P<0.01). Additionally, the ROS content increased and SOD levels decreased significantly (P<0.01). In contrast, treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na2S2O4 treated group (P<0.01). Moreover, Rg1 reduced the levels of caspase3, caspase9, and cytC, while increasing the Bcl2/Bax level. These differences were all statistically significant (P<0.05). Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment, however, Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na2S2O4 treated group (P<0.001). CONCLUSION: The OGD/R process is induced in 661W cells using Na2S2O4. Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway. These results suggest a potential protective effect of Rg1 against retinal I/R injury.

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“…Taken together, pemafibrate could be useful for neuroprotection against various retinal ischemic injuries. A recent report demonstrated that PPARα activation by treatment with fenofibric acid (another PPARα activator) promoted the survival of rat retinal cells against retinal I/R injury 25 . However, the preventive role of pemafibrate against retinal I/R injury in mice remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Retinal degeneration induced in a mouse model of ischemia–reperfusion injury and its management by pemafibrate treatment

et al. 2022

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Retinal ischemia-reperfusion (I/R) injury is a common cause of visual impairment. To date, no effective treatment is available for retinal I/R injury. In addition, the precise pathological mechanisms still need to be established. Recently, pemafibrate, a peroxisome proliferator-activated receptor α (PPARα) modulator, was shown to be a promising drug for retinal ischemia. However, the role of pemafibrate in preventing retinal I/R injury has not been documented. Here, we investigated how retinal degeneration occurs in a mouse model of retinal I/R injury by elevation of intraocular pressure and examined whether pemafibrate could be beneficial against retinal degeneration. Adult mice were orally administered pemafibrate (0.5 mg/kg/day) for 4 days, followed by retinal I/R injury.The mice were continuously administered pemafibrate once every day until the end of the experiments. Retinal functional changes were measured using electroretinography. Retina, liver, and serum samples were used for western blotting, quantitative PCR, immunohistochemistry, or enzyme linked immunosorbent assay. Retinal degeneration induced by retinal inflammation was prevented by pemafibrate administration. Pemafibrate administration increased the hepatic PPARα target gene expression and serum levels of fibroblast growth factor 21, a neuroprotective molecule in the eye. The expression of hypoxia-response and pro-and anti-apoptotic/inflammatory genes increased in the retina following retinal I/R injury; however, these changes were modulated by pemafibrate administration. In conclusion, pemafibrate is a promising preventive drug for ischemic retinopathies.

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Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas

Cited by 6 publications

References 51 publications

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

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

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

Retinal degeneration induced in a mouse model of ischemia–reperfusion injury and its management by pemafibrate treatment

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