title: Neuroprotectin D1 attenuates laser-induced choroidal neovascularization in mouse.
abstract: OBJECTIVE
  To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation.
  
  
  METHODS
  C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers.
  
  
  RESULTS
  At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days.
  
  
  CONCLUSIONS
  NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-kappaB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be effective after treatment is concluded, suggesting sustained protection and highlighting the potential applicability of this lipid mediator in preventing or ameliorating endothelial cell growth in pathoangiogenesis.
authors.affiliation: Department of Ophthalmology and the Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Sheets
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Monica K
authors.initials: MK
authors.lastname: Ertel
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Knott
authors.forename: Cornelius E
authors.initials: CE
authors.lastname: Regan
authors.forename: Jasmine R
authors.initials: JR
authors.lastname: Elison
authors.forename: William C
authors.initials: WC
authors.lastname: Gordon
authors.forename: Per
authors.initials: P
authors.lastname: Gjorstrup
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000139:chemically induced / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D019793:Fluorescein / Q000378:metabolism; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007834:Lasers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D012160:Retina / Q000187:drug effects / Q000473:pathology
chemical_list: C487679:protectin D1; D004281:Docosahexaenoic Acids; D019793:Fluorescein