Combination of Peroxisome Proliferator-Activated Receptor (PPAR) Alpha and Gamma Agonists Prevents Corneal Inflammation and Neovascularization in a Rat Alkali Burn Model

Nakano, Yuji; Arima, Takeshi; Tobita, Yutaro; Uchiyama, Masaaki; Shimizu, Akira; Takahashi, Hiroshi

doi:10.3390/ijms21145093

Cited by 18 publications

(21 citation statements)

References 42 publications

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“…This implies PPARα activation could have potential for use as a preventive agent in patients with high risk of dry eye. Other cornea studies indicated therapeutic roles of PPARα agonists against corneal inflammation and neovascularization [ 110 , 111 ]. Corneal neovascularization is closely related to a reduction in corneal transparency which is important for visual acuity [ 112 , 113 ].…”

Section: Functions Of Pparα In the Eyementioning

confidence: 99%

“…Corneal neovascularization is closely related to a reduction in corneal transparency which is important for visual acuity [ 112 , 113 ]. In rat corneal alkali burn models, corneal neovascularization was seen and a topical injection of fenofibrate suppressed its neovascularization through upregulation of PPARα mRNA expression and suppression of IL-6, IL-1β, Vegf and Ang-2 mRNA expressions [ 110 , 111 ].…”

Section: Functions Of Pparα In the Eyementioning

confidence: 99%

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PPARα Agonist Oral Therapy in Diabetic Retinopathy

2020

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Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.

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Section: Functions Of Pparα In the Eyementioning

confidence: 99%

Section: Functions Of Pparα In the Eyementioning

confidence: 99%

PPARα Agonist Oral Therapy in Diabetic Retinopathy

2020

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“…In ophthalmology, PPARs have recently been reported to affect inflammation, fibrosis, and angiogenesis [13,14,18,19]. However, there are few reports of the effects of PPARs on corneal epithelial wound healing.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of all subtypes of PPARs has been reported to suppress inflammation via inhibition of NF-κB [9,10]. In the field of ophthalmology, we previously reported the anti-inflammatory and anti-neovascular effects of PPARα and PPARγ in a corneal wound model [11][12][13]. On the other hand, our recent study showed that PPARβ/δ promotes neovascularization while suppressing inflammation [14].…”

Section: Introductionmentioning

confidence: 99%

Effects of Selective Peroxisome Proliferator Activated Receptor Agonists on Corneal Epithelial Wound Healing

et al. 2021

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The effects of each subtype-selective peroxisome proliferator activated receptor (PPAR) agonist (α, β/δ, γ) on corneal epithelial wound healing were investigated using a rat corneal alkali burn model. After the alkali burn, each PPAR agonist or vehicle ophthalmic solution was instilled topically onto the rat’s cornea. Corneal epithelial healing processes were evaluated by fluorescein staining. Pathological analyses and real-time reverse transcription polymerase chain reactions were performed to evaluate Ki67 (proliferative maker) expression and inflammatory findings. The area of the corneal epithelial defect at 12 h and 24 h after the alkali burn was significantly smaller in each PPAR group than in the vehicle group. Ki67 mRNA expression was increased in the PPARβ/δ group, whereas mRNA expressions of inflammatory cytokines were suppressed in all of the PPAR agonist groups. Nuclear factor kappa B (NF-κB) was the most suppressed in the PPARγ group. The accelerated corneal epithelial healing effects of each PPAR ligand were thought to be related to the promotion of proliferative capacity and inhibition of inflammation.

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“…Fenofibrate treatment suppressed corneal neovascularization by reducing Vegf and Ang-2 mRNA expressions in a rat corneal alkali burn model [105]. The same group demonstrated that treatment with a mixture of fenofibrate/pioglitazone (combination of PPARα and PPARγ activation) also suppressed corneal neovascularization by reducing Vegf and Ang-2 mRNA expressions in a rat alkali burn model [106]. Another group showed that the oral administration of PPARα agonists (fenofibrate, WY14,643, ETYA, bezafibrate, and gemfibrozil) suppressed FGF2-induced corneal neovascularization [107].…”

Section: Eye Diseasesmentioning

confidence: 94%

PPARα Modulation-Based Therapy in Central Nervous System Diseases

Lee

Tomita

Allen

et al. 2021

Life

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The burden of neurodegenerative diseases in the central nervous system (CNS) is increasing globally. There are various risk factors for the development and progression of CNS diseases, such as inflammatory responses and metabolic derangements. Thus, curing CNS diseases requires the modulation of damaging signaling pathways through a multitude of mechanisms. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors (PPARα, PPARβ/δ, and PPARγ), and they work as master sensors and modulators of cellular metabolism. In this regard, PPARs have recently been suggested as promising therapeutic targets for suppressing the development of CNS diseases and their progressions. While the therapeutic role of PPARγ modulation in CNS diseases has been well reviewed, the role of PPARα modulation in these diseases has not been comprehensively summarized. The current review focuses on the therapeutic roles of PPARα modulation in CNS diseases, including those affecting the brain, spinal cord, and eye, with recent advances. Our review will enable more comprehensive therapeutic approaches to modulate PPARα for the prevention of and protection from various CNS diseases.

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Combination of Peroxisome Proliferator-Activated Receptor (PPAR) Alpha and Gamma Agonists Prevents Corneal Inflammation and Neovascularization in a Rat Alkali Burn Model

Cited by 18 publications

References 42 publications

PPARα Agonist Oral Therapy in Diabetic Retinopathy

PPARα Agonist Oral Therapy in Diabetic Retinopathy

Effects of Selective Peroxisome Proliferator Activated Receptor Agonists on Corneal Epithelial Wound Healing

PPARα Modulation-Based Therapy in Central Nervous System Diseases

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