title: A mouse model of in vivo chemical inhibition of retinal calcium-independent phospholipase A2 (iPLA2).
abstract: Numerous studies have reported the implication of calcium-independent phospholipase A2 (iPLA2) in various biological mechanisms. Most of these works have used in vitro models and only a few have been carried out in vivo on iPLA2(-/-) mice. The functions of iPLA2 have been investigated in vivo in the heart, brain, pancreatic islets, and liver, but not in the retina despite its very high content in phospholipids. Phospholipids in the retina are known to be involved in several various key mechanisms such as visual transduction, inflammation or apoptosis. In order to investigate the implication of iPLA2 in these processes, this work was aimed to build an in vivo model of iPLA2 activity inhibition. After testing the efficacy of different chemical inhibitors of iPLA2, we have validated the use of bromoenol lactone (BEL) in vitro and in vivo for inhibiting the activity of iPLA2. Under in vivo conditions, a dose of 6μg/g of body weight of BEL in mice displayed a 50%-inhibition of retinal iPLA2 activity 8-16h after intraperitoneal administration. Delivering the same dose twice a day to animals was successful in producing a similar inhibition that was stable over one week. In summary, this novel mouse model exhibits a significant inhibition of retinal iPLA2 activity. This model of chemical inhibition of iPLA2 will be useful in future studies focusing on iPLA2 functions in the retina.
authors.affiliation: CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, F-21000 Dijon, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Saab-Aoudé
authors.forename: Alain M
authors.initials: AM
authors.lastname: Bron
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Creuzot-Garcher
authors.forename: Lionel
authors.initials: L
authors.lastname: Bretillon
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors*; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012160:Retina / Q000201:enzymology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse