Abstract
The effects of peroxisome proliferator-activated receptor (PPAR)β/δ ophthalmic solution were investigated in a rat corneal alkali burn model. After alkali injury, GW501516 (PPARβ/δ agonist) or vehicle ophthalmic solution was topically instilled onto the rat’s cornea twice a day until day 7. Pathological findings were evaluated, and real-time reverse transcription polymerase chain reaction was performed. GW501516 strongly suppressed infiltration of neutrophils and pan-macrophages, and reduced the mRNA expression of interleukin-6, interleukin-1β, tumor necrosis factor alpha, and nuclear factor-kappa B. On the other hand, GW501516 promoted infiltration of M2 macrophages, infiltration of vascular endothelial cells associated with neovascularization in the wounded area, and expression of vascular endothelial growth factor A mRNA. However, 7-day administration of GW501516 did not promote neovascularization in uninjured normal corneas. Thus, the PPARβ/δ ligand suppressed inflammation and promoted neovascularization in the corneal wound healing process. These results will help to elucidate the role of PPARβ/δ in the field of ophthalmology.
Highlights
Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor [1,2]
We investigated the characteristics of GW501516, a PPARβ/δ ligand, and explored the therapeutic effects of an ophthalmic solution of a PPARβ/δ agonist using a rat alkali burn model
Less infiltration of inflammatory cells was observed (Figure 1q) and more neovascularization was seen in the PPARβ/δ group compared to the vehicle group (Figure 1d,h,l,p)
Summary
Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor [1,2]. PPAR has three subtypes, α, β (δ), and γ, each of which is activated by a specific ligand and controls expression of various genes by binding to the regulatory region of the target gene [1]. PPARβ/δ is expressed in many tissues and organs such as skeletal muscle, adipose tissue, the cardiovascular system, the uterus after implantation, intestine, brain, and skin, and is involved in many important functions, such as energy metabolism, cell differentiation and proliferation, tissue repair, and cancer progression, suggesting its potential as a therapeutic target [2,6,7]. In addition to these basic functions, PPARs are anti-inflammatory [8]. We investigated the characteristics of GW501516, a PPARβ/δ ligand, and explored the therapeutic effects of an ophthalmic solution of a PPARβ/δ agonist using a rat alkali burn model
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