PMID- 30547709
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20200629
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Linking)
VI  - 35
IP  - 2
DP  - 2019 Mar
TI  - In Vivo Choroidal Neovascularization and Macrophage Studies Provide Further 
      Evidence for a Broad Role of Prostacyclin in Angiogenesis.
PG  - 98-105
LID - 10.1089/jop.2018.0077 [doi]
AB  - PURPOSE: The purpose of these studies was (1) to investigate the ability of human 
      M1 phenotype macrophages to secrete vascular endothelial growth factor (VEGF) and 
      the influence of prostacyclin receptor (IP) stimulation (2) to evaluate the 
      contribution of the proangiogenic prostanoid prostacyclin to experimental 
      choroidal neovascularization Methods: Human macrophages derived from primary 
      blood mononuclear cells were functionally biased toward the M1 phenotype by using 
      tumor necrosis factor alpha (TNFalpha). Experimental choroidal neovascularization was 
      produced by laser photocoagulation. Antagonist drugs RO-3244794 (IP antagonist) 
      and GW 627368 (EP(4) antagonist) were administered according to an optimal dosing 
      regimen that was predetermined by bioavailability studies. RESULTS: IP receptor 
      stimulation had diametrically opposed effects on VEGF release compared with 
      reported data on cytokine/chemokine secretion from human macrophages. For 
      example, the IP agonist cicaprost stimulated VEGF secretion although it inhibits 
      monocyte chemoattractant protein-1 (MCP-1) secretion: both would favor a 
      proangiogenic effect. The IP receptor antagonist RO-3244794 produced an  approximately 20% 
      statistically significant reduction in the neovascularized lesion area in the 
      choroidal neovascularization model, which was a similar level to that produced by 
      the EP(4) antagonist GW 627368. Combining the 2 drugs produced a statistically 
      significant reduction in neovascularization but only of slightly greater 
      magnitude than that obtained with each antagonist administered alone. 
      CONCLUSIONS: IP receptor stimulation potently and highly efficaciously promoted 
      VEGF release from human M1 macrophages, indicating a possible contribution of the 
      M1 macrophage subtype to VEGF-induced choroidal neovascularization. Studies in 
      living animals suggest that prostacyclin and its target IP receptor contribute to 
      choroidal neovascularization, although to a more modest extent than might have 
      been expected.
FAU - Woodward, David F
AU  - Woodward DF
AD  - Department of Biological Sciences, Allergan, Inc. , Irvine, California.
FAU - Wang, Jenny W
AU  - Wang JW
AD  - Department of Biological Sciences, Allergan, Inc. , Irvine, California.
FAU - Ni, Ming
AU  - Ni M
AD  - Department of Biological Sciences, Allergan, Inc. , Irvine, California.
FAU - Bauer, Alex J
AU  - Bauer AJ
AD  - Department of Biological Sciences, Allergan, Inc. , Irvine, California.
FAU - Poloso, Neil J
AU  - Poloso NJ
AD  - Department of Biological Sciences, Allergan, Inc. , Irvine, California.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181214
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Antihypertensive Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis/deficiency/metabolism
MH  - Choroidal Neovascularization/*drug therapy/metabolism/pathology
MH  - Disease Models, Animal
MH  - Epoprostenol/*pharmacology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Ophthalmic Solutions/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vascular Endothelial Growth Factors/analysis/metabolism
OTO - NOTNLM
OT  - VEGF
OT  - choroid
OT  - neovascularization
OT  - prostacyclin
OT  - prostaglandin E
OT  - retina
EDAT- 2018/12/15 06:00
MHDA- 2020/07/01 06:00
CRDT- 2018/12/15 06:00
PHST- 2018/12/15 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2018/12/15 06:00 [entrez]
AID - 10.1089/jop.2018.0077 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2019 Mar;35(2):98-105. doi: 10.1089/jop.2018.0077. Epub 
      2018 Dec 14.