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

2021 ◽  
Vol 14 (2) ◽  
pp. 88
Author(s):  
Yutaro Tobita ◽  
Takeshi Arima ◽  
Yuji Nakano ◽  
Masaaki Uchiyama ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Vehicle Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Corneal Epithelial ◽  
Ppar Agonist ◽  
Alkali Burn ◽  
Epithelial Wound Healing ◽  
Epithelial Healing

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.

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

2020 ◽  
Vol 21 (14) ◽  
pp. 5093
Author(s):  
Yuji Nakano ◽  
Takeshi Arima ◽  
Yutaro Tobita ◽  
Masaaki Uchiyama ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ophthalmic Solution ◽  
Inflammatory Cells ◽  
Vehicle Group ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alkali Burn ◽  
Pparγ Agonist ◽  
Pparγ Agonists

Peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) agonists have anti-inflammatory and anti-neovascularization effects, but few reports have tested the combination of PPARα and PPARγ agonists. In this study, we investigated the therapeutic effects of ophthalmic solutions of agonists of PPARα, PPARγ, and the combination in a rat corneal alkali burn model. After alkali injury, an ophthalmic solution of 0.05% fenofibrate (PPARα group), 0.1% pioglitazone (PPARγ group), 0.05% fenofibrate + 0.1% pioglitazone (PPARα+γ group), or vehicle (vehicle group) was topically instilled onto the rat’s cornea twice a day. After instillation, upregulation was seen of PPAR mRNA corresponding to each agonist group. Administration of agonists for PPARα, PPARγ, and PPARα+γ suppressed inflammatory cells, neovascularization, and fibrotic changes. In addition, the PPARγ agonist upregulated M2 macrophages, which contributed to wound healing, whereas the PPARα agonist suppressed immature blood vessels in the early phase. Administration of PPARα+γ agonists showed therapeutic effects in corneal wound healing, combining the characteristics of both PPARα and PPARγ agonists. The results indicate that the combination of PPARα and γ agonists may be a new therapeutic strategy.

Effect of Doxycycline Hyclate on Corneal Epithelial Wound Healing in the Rabbit Alkali-Burn Model

Cornea ◽  
1993 ◽  
Vol 12 (5) ◽  
pp. 379-382 ◽  
Author(s):  
Henry D. Perry ◽  
Leon W. Hodes ◽  
John A. Seedor ◽  
Eric D. Donnenfeld ◽  
Thomas F. McNamara ◽  
...  
Keyword(s):  
Wound Healing ◽  
Doxycycline Hyclate ◽  
Corneal Epithelial ◽  
Alkali Burn ◽  
Epithelial Wound Healing

Role of the C Domain of IGFs in Synergistic Promotion, with a Substance P–Derived Peptide, of Rabbit Corneal Epithelial Wound Healing

2004 ◽  
Vol 45 (4) ◽  
pp. 1125 ◽  
Author(s):  
Naoyuki Yamada ◽  
Ryoji Yanai ◽  
Masatsugu Nakamura ◽  
Makoto Inui ◽  
Teruo Nishida
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

WY-14 643, a Selective PPARα Agonist, Induces Proinflammatory and Proangiogenic Responses in Human Ocular Cells

2010 ◽  
Vol 29 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Jin-Zhong Zhang ◽  
Keith W. Ward
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Peroxisome Proliferator ◽  
Cytokine Release ◽  
Corneal Epithelial Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Corneal Epithelial ◽  
Factor Α ◽  
Endothelial Growth Factor ◽  
Pparα Agonist

Peroxisome proliferator-activated receptor α (PPARα) agonism in ocular inflammation has not been thoroughly investigated. The objective of this investigation was to determine the effect of WY-14 643, a selective PPARα agonist, on inflammatory cytokine release in human ocular cells. Stimulation of primary human corneal epithelial cells, keratocytes, and retinal endothelial cells with 1 to 10 ng/mL interleukin 1β (IL-1β) resulted in a significant increase in numerous inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor α (TNF-α); and dexamethasone was able to significantly inhibit these effects. However, WY-14 643 did not effectively block IL-1β-induced cytokine release in ocular cells; rather, significant increases in IL-1β-induced inflammatory cytokines were observed in these cells but not in aortic smooth muscle cells. WY-14 643 also significantly upregulated vascular endothelial growth factor (VEGF) expression in corneal epithelial cells and keratocytes. These studies demonstrate for the first time that PPARα agonism may be proinflammatory and proangiogenic in a variety of ocular cells and suggest that therapeutic applications of such agents in ophthalmology may be limited.

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