Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization

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.

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

“…I-κBα inhibits NF-kB nuclear translocation and restricts transcription downstream of the NF-κB signaling pathway [24]. Previous studies have reported that PPARα and PPARβ/δ suppress NF-κB [9,11,14]. In the present research, immunostaining and cell counting analyses showed that all PPAR subtypes suppressed NF-κB expression.…”

“…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.…”

“…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]. We reported that each subtype of PPAR is localized differently in the eye [15].…”

PPARβ/δ Agonist Alleviates Diabetic Osteoporosis via Regulating M1/M2 Macrophage Polarization

“…Treatment with LPS-induced M1 macrophage culture supernatant stimulated the osteoclastogenesis (Zhang et al, 2021). PPARβ/δ agonist has been found to reduce the expression of inflammatory factors such as IL-1β and IL-6 by inhibiting NF-κB signaling (Rival et al, 2002;Bishop-Bailey and Bystrom, 2009;Coll et al, 2010), and promote the recruitment of M2 macrophages to accelerate the injury repair process (Tobita et al, 2020). However, its role in diabetic osteoporosis has not been reported yet.…”

CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing

“…The functional role of PPAR expression in ocular and periocular tissues has been described to be linked to the regulation of the local immune-inflammatory, fibrogenic and neo-angiogenic process [ 57 ].…”