VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.

Although blocking VEGF has a positive effect in wet age-related macular degeneration (AMD), the effect of blocking its receptors remains unclear. This was an investigation of the effect of VEGF receptor (VEGFR) 1 and/or 2 blockade on retinal microglia/macrophage infiltration in laser-induced choroid...

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Autores principales:	Hu Huang, Rachel Parlier, Ji-Kui Shen, Gerard A Lutty, Stanley A Vinores
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42226e624b854595b5a48728779ba17c
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spelling	oai:doaj.org-article:42226e624b854595b5a48728779ba17c2021-11-18T08:58:48ZVEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.1932-620310.1371/journal.pone.0071808https://doaj.org/article/42226e624b854595b5a48728779ba17c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977149/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Although blocking VEGF has a positive effect in wet age-related macular degeneration (AMD), the effect of blocking its receptors remains unclear. This was an investigation of the effect of VEGF receptor (VEGFR) 1 and/or 2 blockade on retinal microglia/macrophage infiltration in laser-induced choroidal neovascularization (CNV), a model of wet AMD. CNV lesions were isolated by laser capture microdissection at 3, 7, and 14 days after laser and analyzed by RT-PCR and immunofluorescence staining for mRNA and protein expression, respectively. Neutralizing antibodies for VEGFR1 or R2 and the microglia inhibitor minocycline were injected intraperitoneally (IP). Anti-CD11b, CD45 and Iba1 antibodies were used to confirm the cell identity of retinal microglia/macrophage, in the RPE/choroidal flat mounts or retinal cross sections. CD11b(+), CD45(+) or Iba1(+) cells were counted. mRNA of VEGFR1 and its three ligands, PlGF, VEGF-A (VEGF) and VEGF-B, were expressed at all stages, but VEGFR2 were detected only in the late stage. PlGF and VEGF proteins were expressed at 3 and 7 days after laser. Anti-VEGFR1 (MF1) delivered IP 3 days after laser inhibited infiltration of leukocyte populations, largely retinal microglia/macrophage to CNV, while anti-VEGFR2 (DC101) had no effect. At 14 days after laser, both MF1 and DC101 antibodies markedly inhibited retinal microglia/macrophage infiltration into CNV. Therefore, VEGFR1 and R2 play differential roles in the pathogenesis of CNV: VEGFR1 plays a dominant role at 3 days after laser; but both receptors play pivotal roles at 14 days after laser. In vivo imaging demonstrated accumulation of GFP-expressing microglia into CNV in both CX3CR1(gfp/gfp) and CX3CR1(gfp/+) mice. Minocycline treatment caused a significant increase in lectin(+) cells in the sub-retinal space anterior to CNV and a decrease in dextran-perfused neovessels compared to controls. Targeting the chemoattractant molecules that regulate trafficking of retinal microglia/macrophage appears to be a compelling therapeutic strategy to control CNV and treat wet AMD.Hu HuangRachel ParlierJi-Kui ShenGerard A LuttyStanley A VinoresPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71808 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hu Huang Rachel Parlier Ji-Kui Shen Gerard A Lutty Stanley A Vinores VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
description	Although blocking VEGF has a positive effect in wet age-related macular degeneration (AMD), the effect of blocking its receptors remains unclear. This was an investigation of the effect of VEGF receptor (VEGFR) 1 and/or 2 blockade on retinal microglia/macrophage infiltration in laser-induced choroidal neovascularization (CNV), a model of wet AMD. CNV lesions were isolated by laser capture microdissection at 3, 7, and 14 days after laser and analyzed by RT-PCR and immunofluorescence staining for mRNA and protein expression, respectively. Neutralizing antibodies for VEGFR1 or R2 and the microglia inhibitor minocycline were injected intraperitoneally (IP). Anti-CD11b, CD45 and Iba1 antibodies were used to confirm the cell identity of retinal microglia/macrophage, in the RPE/choroidal flat mounts or retinal cross sections. CD11b(+), CD45(+) or Iba1(+) cells were counted. mRNA of VEGFR1 and its three ligands, PlGF, VEGF-A (VEGF) and VEGF-B, were expressed at all stages, but VEGFR2 were detected only in the late stage. PlGF and VEGF proteins were expressed at 3 and 7 days after laser. Anti-VEGFR1 (MF1) delivered IP 3 days after laser inhibited infiltration of leukocyte populations, largely retinal microglia/macrophage to CNV, while anti-VEGFR2 (DC101) had no effect. At 14 days after laser, both MF1 and DC101 antibodies markedly inhibited retinal microglia/macrophage infiltration into CNV. Therefore, VEGFR1 and R2 play differential roles in the pathogenesis of CNV: VEGFR1 plays a dominant role at 3 days after laser; but both receptors play pivotal roles at 14 days after laser. In vivo imaging demonstrated accumulation of GFP-expressing microglia into CNV in both CX3CR1(gfp/gfp) and CX3CR1(gfp/+) mice. Minocycline treatment caused a significant increase in lectin(+) cells in the sub-retinal space anterior to CNV and a decrease in dextran-perfused neovessels compared to controls. Targeting the chemoattractant molecules that regulate trafficking of retinal microglia/macrophage appears to be a compelling therapeutic strategy to control CNV and treat wet AMD.
format	article
author	Hu Huang Rachel Parlier Ji-Kui Shen Gerard A Lutty Stanley A Vinores
author_facet	Hu Huang Rachel Parlier Ji-Kui Shen Gerard A Lutty Stanley A Vinores
author_sort	Hu Huang
title	VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
title_short	VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
title_full	VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
title_fullStr	VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
title_full_unstemmed	VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.
title_sort	vegf receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced cnv.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/42226e624b854595b5a48728779ba17c
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VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration into laser-induced CNV.

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