PMID- 28107458
OWN - NLM
STAT- MEDLINE
DCOM- 20170810
LR  - 20240327
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 1
DP  - 2017
TI  - Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation.
PG  - e0169865
LID - 10.1371/journal.pone.0169865 [doi]
LID - e0169865
AB  - PURPOSE: Inhibiting VEGF is the gold standard treatment for neovascular 
      age-related macular degeneration (AMD). It is also effective in preventing 
      retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and 
      retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and 
      many other growth factors, and therefore a possible alternative drug target in 
      intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an 
      inducible, endothelial specific knock out model for Nrp1. METHODS: Crossing Nrp1 
      floxed mice with Pdgfb-CreERT2 mice produced tamoxifen-inducible, endothelial 
      specific Nrp1 knock out mice (Nrp1DeltaEC) and Cre-negative, control littermates. 
      Cre-recombinase activity was confirmed in the Ai3(RCL-EYFP) reporter strain. 
      Animals were subjected to laser-induced CNV (532 nm) and spectral domain-optical 
      coherence tomography (SD-OCT) was performed immediately after laser and at day 7. 
      Fluorescein angiography (FA) evaluated leakage and postmortem lectin staining in 
      flat mounted RPE/choroid complexes was also used to measure CNV. Furthermore, 
      retinal neovascularisation in the oxygen induced retinopathy (OIR) model was 
      assessed by immunohistochemistry in retinal flatmounts. RESULTS: In vivo FA, OCT 
      and post-mortem lectin staining showed a statistically significant reduction in 
      leakage (p<0.05), CNV volume (p<0.05) and CNV area (p<0.05) in the Nrp1DeltaEC mice 
      compared to their Cre-negative littermates. Also the OIR model showed reduced 
      retinal NV in the mutant animals compared to wild types (p<0.001). CONCLUSION: We 
      have demonstrated reduced choroidal and retinal NV in animals that lack 
      endothelial Nrp1, confirming a role of Nrp1 in those processes. Therefore, Nrp1 
      may be a promising drug target for neovascular diseases in the eye.
FAU - Fernandez-Robredo, Patricia
AU  - Fernandez-Robredo P
AD  - UCL Institute of Ophthalmology, University College London, London, United 
      Kingdom.
AD  - Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, 
      IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
FAU - Selvam, Senthil
AU  - Selvam S
AD  - UCL Institute of Ophthalmology, University College London, London, United 
      Kingdom.
FAU - Powner, Michael B
AU  - Powner MB
AD  - UCL Institute of Ophthalmology, University College London, London, United 
      Kingdom.
AD  - Division of Optometry and Visual Science, School of Health Sciences, City 
      University London, London, United Kingdom.
FAU - Sim, Dawn A
AU  - Sim DA
AD  - UCL Institute of Ophthalmology, University College London, London, United 
      Kingdom.
AD  - NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS 
      Foundation Trust, London, United Kingdom.
FAU - Fruttiger, Marcus
AU  - Fruttiger M
AD  - UCL Institute of Ophthalmology, University College London, London, United 
      Kingdom.
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20170120
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 144713-63-3 (Neuropilin-1)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
SB  - IM
MH  - Animals
MH  - Choroidal Neovascularization/*physiopathology
MH  - Fluorescein Angiography
MH  - Integrases/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neuropilin-1/genetics/*physiology
MH  - Retinal Neovascularization/*physiopathology
PMC - PMC5249189
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/01/21 06:00
MHDA- 2017/08/11 06:00
PMCR- 2017/01/20
CRDT- 2017/01/21 06:00
PHST- 2016/03/15 00:00 [received]
PHST- 2016/12/23 00:00 [accepted]
PHST- 2017/01/21 06:00 [entrez]
PHST- 2017/01/21 06:00 [pubmed]
PHST- 2017/08/11 06:00 [medline]
PHST- 2017/01/20 00:00 [pmc-release]
AID - PONE-D-16-10803 [pii]
AID - 10.1371/journal.pone.0169865 [doi]
PST - epublish
SO  - PLoS One. 2017 Jan 20;12(1):e0169865. doi: 10.1371/journal.pone.0169865. 
      eCollection 2017.