Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice.

Angiogenesis
Yohei TomitaLois E H Smith

Abstract

To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4+/+) and knock out (Ffar4-/-) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-ĸB/NF-ĸB and qRT-PCR for Il-6, Il-1β, Tnf-α, Vegf, and Nf-ĸb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4+/+ and Ffar4-/- mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4-/- compared to Ffar4+/+ mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1β) ...Continue Reading

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Citations

Oct 26, 2020·Diabetologia·Yohei TomitaYoshihiko Usui
Mar 9, 2021·ACS Omega·Faith Pwaniyibo SamsonWan Jin Jahng
Apr 13, 2021·Journal of Medicinal Chemistry·Gabriele CarulloAntonella Brizzi
Jun 15, 2021·The American Journal of Pathology·Seoung-Woo LeeJin-Kyu Park

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