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Qian Chen, Sihao Ye, Nan Jiang, rongrong zong, Zuguo Liu; Palmitoylethanolamide treatment suppresses Müller cell activation in a mouse model of proliferative retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1646. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Müller cell is an important source of cytokines and inflammatory factors in proliferative retinopathy and retinal degeneration. The purpose of this study is to test the effects of palmitoylethanolamide (PEA), an endogenous peroxisome proliferator-activated receptor alpha (PPARα) agonist, on Müller cell activation and Müller cell-releasing cytokines in proliferative retinopathy, and to determine its molecular mechanism of action.
The rat Müller cell line rMC-1 and a mouse model of oxygen induced retinopathy (OIR) were used in this study. PEA was intraperitoneally injected into OIR mice from P12 to P17. The Müller cell activation marker GFAP was measured by RT-RCR and Western blot analysis. The inflammatory cytokines such as TNFα, VCAM-1, ICAM-1 and VEGF were evaluated by Western blot analysis and immunohistochemistry. TUNEL assay was used to detect apoptotic cells. The blood vessels in whole-mount retina were stained by isolectin IB4. Pro-fibrotic cytokine TNF-β2 was measured by RT-PCR and Western blot analysis. Levels of PPARα were measured by RT-PCR and Western blot analysis.
PEA treatment protected rMC-1 cells from apoptosis and reduced levels of inflammatory cytokines TNF-α, ICAM-1, VCAM-1 and VEGF in H2O2 treated rMC-1 cells. In OIR retinas, PEA significantly suppressed Müller cell activation, decreased the expression of TNF-α, ICAM-1 and VEGF in mRNA and protein levels. Meanwhile, PEA protected retinal cells from apoptosis and reduced the avascular regions and neovascularization in OIR retinas. In addition, PEA treatment decreased expression level of Müller cell releasing pro-fibrotic cytokine TNF-β2, and reduced retinal levels of TNF-βRII, phospho-Smad2/3, Smad2/3 and α-SMA. Further, both mRNA and protein levels of PPARα were elevated in the cells and OIR retinas under PEA treatment.
PEA treatment suppresses Müller cell activation and reduces Müller cell mediated cytokines release through increasing the retinal PPARα level. PEA may be potential treatment for retinal diseases associated with retinal gliosis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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