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Akihiro Inoue, Yuka Okada, Ai Kitano, Peter S. Reinach, Nili Parekh, Shizuya Saika; Effects Of Ppar-beta/delta On Migration And Proliferation In Corneal Epithelium. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2041.
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© ARVO (1962-2015); The Authors (2016-present)
To examine if peroxisome proliferator-activated receptor (PPAR)-beta/delta affects corneal epithelial wound healing rates. The PPAR family consists of three members; PPAR alpha,-beta/delta and gamma. They modulate inflammatory responses as well as cell proliferation and migration during epithelial wound healing. We reported that a PPAR-gamma ligand suppresses corneal wound healing (ARVO 2008).
1) Immunohistochemistry validated PPAR-beta/delta protein expression in mouse corneas,2) Scratch Wound Assay was applied in the presence or absence of PPAR beta/delta agonist GW501516 (50-100 nM) and/or antagonist GSK0660 (150 nM- 1.5 µM) to determine their effects on HCEC migration. Wound area at 0 to 36 h was calculated as mean ± SEM using 0 h as baseline. .3) Alamar blue staining evaluated the effects of GW501516 (50-100 nM) and/or GSK0660 (1 µM) on HCEC proliferation.4) Mouse eye globes with a central corneal epithelial defect (n=24) were incubated for 6 - 30 h with either GW501516 (50-100 nM) and/or GSK0660 (1 µM) and time dependence for defect closure was evaluated.
1) The PPAR-beta/delta protein was detected in mouse corneal epithelium. 2) With GW501516, the closure of wound area was significantly accelerated compared to control. 3) GW501516 increased cell proliferation whereas GSK0660 suppressed this response. 4) With GSK0660, wound area closure was significantly inhibited compared to its control.
The PPAR-beta/delta ligand facilitated wound healing in cultured HCEC sheet and in organ cultured eyes. Our results suggest that PPAR- beta/delta activity modulation plays a role in controlling injury-induced increases in corneal epithelial cell migration and proliferation.
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