title: Involvement of plasmalogens in post-natal retinal vascular development.
abstract: OBJECTIVE
  Proper development of retinal blood vessels is essential to ensure sufficient oxygen and nutrient supplies to the retina. It was shown that polyunsaturated fatty acids (PUFAs) could modulate factors involved in tissue vascularization. A congenital deficiency in ether-phospholipids, also termed "plasmalogens", was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered to be reservoirs of PUFAs, we wished to improve our understanding of the mechanisms by which plasmalogens regulate retinal vascular development and whether the release of PUFAs by calcium-independent phospholipase A2 (iPLA2) could be involved.
  
  
  RESULTS
  By characterizing the cellular and molecular steps of retinal vascular development in a mouse model of plasmalogen deficiency, we demonstrated that plasmalogens modulate angiogenic processes during the early phases of retinal vascularization. They influence glial activity and primary astrocyte template formation, endothelial cell proliferation and retinal vessel outgrowth, and impact the expression of the genes involved in angiogenesis in the retina. These early defects led to a disorganized and dysfunctional retinal vascular network at adult age. By comparing these data to those obtained on a mouse model of retinal iPLA2 inhibition, we suggest that these processes may be mediated by PUFAs released from plasmalogens and further signalling through the angiopoietin/tie pathways.
  
  
  CONCLUSIONS
  These data suggest that plasmalogens play a crucial role in retinal vascularization processes.
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors: Sarah
authors: S
authors: Saab
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors: Bénédicte
authors: B
authors: Buteau
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors: Laurent
authors: L
authors: Leclère
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Department of Ophthalmology, University Hospital, Dijon, France.
authors: Alain M
authors: AM
authors: Bron
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Department of Ophthalmology, University Hospital, Dijon, France.
authors: Catherine P
authors: CP
authors: Creuzot-Garcher
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors: Lionel
authors: L
authors: Bretillon
authors: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors: Niyazi
authors: N
authors: Acar
mesh_terms: D000217:Acyltransferases / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D004596:Electroretinography; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010955:Plasmalogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy*; D012171:Retinal Vessels / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D010955:Plasmalogens; D012333:RNA, Messenger; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse