Cargando…

Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)

Purpose: Mononuclear phagocytes (MNPs) are present in neovascular age-related macular degeneration (nv AMD) which is also called choroidal neovascularization (CNV). The number and phenotype of the MNPs depend upon the local environment in the CNV and effect of nv AMD therapy. We investigated ocular...

Descripción completa

Detalles Bibliográficos
Autores principales: Will-Orrego, Adrian, Qiu, Yubin, Fassbender, Elizabeth S., Shen, Siyuan, Aranda, Jorge, Kotagiri, Namrata, Maker, Michael, Liao, Sha-Mei, Jaffee, Bruce D., Poor, Stephen H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152860/
https://www.ncbi.nlm.nih.gov/pubmed/30188257
http://dx.doi.org/10.1089/jop.2017.0131
_version_ 1783357439952814080
author Will-Orrego, Adrian
Qiu, Yubin
Fassbender, Elizabeth S.
Shen, Siyuan
Aranda, Jorge
Kotagiri, Namrata
Maker, Michael
Liao, Sha-Mei
Jaffee, Bruce D.
Poor, Stephen H.
author_facet Will-Orrego, Adrian
Qiu, Yubin
Fassbender, Elizabeth S.
Shen, Siyuan
Aranda, Jorge
Kotagiri, Namrata
Maker, Michael
Liao, Sha-Mei
Jaffee, Bruce D.
Poor, Stephen H.
author_sort Will-Orrego, Adrian
collection PubMed
description Purpose: Mononuclear phagocytes (MNPs) are present in neovascular age-related macular degeneration (nv AMD) which is also called choroidal neovascularization (CNV). The number and phenotype of the MNPs depend upon the local environment in the CNV and effect of nv AMD therapy. We investigated ocular cell infiltration and conditions that modulate angiogenesis in a laser-induced mouse CNV model. Methods: We developed assays to quantify MNPs in our established mouse CNV model. One MNP assay quantified the number of subretinal cells peripheral to the CNV lesions. A second assay semiquantitatively assesses the number of MNPs localized to the CNV lesion. We used these assays to measure the effect of toll-like receptor-2 (TLR-2) activation, anti-vascular endothelial growth factor (VEGF) therapy, and chemokine (C-C motif) ligand 2 (Ccl2) genetic deletion on MNP infiltration after laser injury. Results: Laser injury induced blood vessel growth and infiltration of MNPs. Systemic administration of a TLR-2 activating peptide increased laser-induced CNV area, MNP cell numbers, and MNP density over the CNV lesions. Systemic administration of a VEGF antibody reduced CNV area, while Ccl2 genetic deletion increased CNV area. Despite the change in amount of angiogenesis, MNP infiltration was, surprisingly, unchanged in these 2 conditions. Conclusions: MNP quantification provides biological insights for candidate AMD therapies. The number of infiltrating MNP cells does not correlate with the amount of laser-induced CNV area.
format Online
Article
Text
id pubmed-6152860
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Mary Ann Liebert, Inc., publishers
record_format MEDLINE/PubMed
spelling pubmed-61528602018-09-25 Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV) Will-Orrego, Adrian Qiu, Yubin Fassbender, Elizabeth S. Shen, Siyuan Aranda, Jorge Kotagiri, Namrata Maker, Michael Liao, Sha-Mei Jaffee, Bruce D. Poor, Stephen H. J Ocul Pharmacol Ther Original Articles Purpose: Mononuclear phagocytes (MNPs) are present in neovascular age-related macular degeneration (nv AMD) which is also called choroidal neovascularization (CNV). The number and phenotype of the MNPs depend upon the local environment in the CNV and effect of nv AMD therapy. We investigated ocular cell infiltration and conditions that modulate angiogenesis in a laser-induced mouse CNV model. Methods: We developed assays to quantify MNPs in our established mouse CNV model. One MNP assay quantified the number of subretinal cells peripheral to the CNV lesions. A second assay semiquantitatively assesses the number of MNPs localized to the CNV lesion. We used these assays to measure the effect of toll-like receptor-2 (TLR-2) activation, anti-vascular endothelial growth factor (VEGF) therapy, and chemokine (C-C motif) ligand 2 (Ccl2) genetic deletion on MNP infiltration after laser injury. Results: Laser injury induced blood vessel growth and infiltration of MNPs. Systemic administration of a TLR-2 activating peptide increased laser-induced CNV area, MNP cell numbers, and MNP density over the CNV lesions. Systemic administration of a VEGF antibody reduced CNV area, while Ccl2 genetic deletion increased CNV area. Despite the change in amount of angiogenesis, MNP infiltration was, surprisingly, unchanged in these 2 conditions. Conclusions: MNP quantification provides biological insights for candidate AMD therapies. The number of infiltrating MNP cells does not correlate with the amount of laser-induced CNV area. Mary Ann Liebert, Inc., publishers 2018-09-01 2018-09-01 /pmc/articles/PMC6152860/ /pubmed/30188257 http://dx.doi.org/10.1089/jop.2017.0131 Text en © Adrian Will-Orrego et al., 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited.
spellingShingle Original Articles
Will-Orrego, Adrian
Qiu, Yubin
Fassbender, Elizabeth S.
Shen, Siyuan
Aranda, Jorge
Kotagiri, Namrata
Maker, Michael
Liao, Sha-Mei
Jaffee, Bruce D.
Poor, Stephen H.
Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title_full Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title_fullStr Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title_full_unstemmed Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title_short Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV)
title_sort amount of mononuclear phagocyte infiltrate does not predict area of experimental choroidal neovascularization (cnv)
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152860/
https://www.ncbi.nlm.nih.gov/pubmed/30188257
http://dx.doi.org/10.1089/jop.2017.0131
work_keys_str_mv AT willorregoadrian amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT qiuyubin amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT fassbenderelizabeths amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT shensiyuan amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT arandajorge amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT kotagirinamrata amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT makermichael amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT liaoshamei amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT jaffeebruced amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv
AT poorstephenh amountofmononuclearphagocyteinfiltratedoesnotpredictareaofexperimentalchoroidalneovascularizationcnv