title: Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation.
abstract: OBJECTIVE
  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 (Nrp1ΔEC) 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 Nrp1ΔEC 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.|Experimental Ophthalmology Laboratory, School of Medicine, University of Navarra, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Robredo
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Senthil
authors.initials: S
authors.lastname: Selvam
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.|Division of Optometry and Visual Science, School of Health Sciences, City University London, London, United Kingdom.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Powner
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.|NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Sim
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fruttiger
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000503:physiopathology*; D005451:Fluorescein Angiography; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000235:genetics / Q000502:physiology*; D015861:Retinal Neovascularization / Q000503:physiopathology*
chemical_list: D039942:Neuropilin-1; C045073:Cre recombinase; D019426:Integrases