title: Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat.
abstract: OBJECTIVE
  We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy.
  
  
  METHODS
  Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg(-1) day(-1), pump), or diabetic + lisinopril (10 mg kg(-1) day(-1), drinking water) rats were evaluated over 16 weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg(-1) day(-1), pump) or lisinopril (10 mg kg(-1) day(-1), drinking water) was administered during retinopathy development between postnatal days 12 and 18.
  
  
  RESULTS
  Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg(-1) day(-1) aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg(-1) day(-1) aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg(-1) day(-1) aliskiren and normalised by 30 mg kg(-1) day(-1) aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels.
  
  
  CONCLUSIONS
  Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.
authors.affiliation: Department of Immunology, Monash University, Alfred Medical Research and Education Precinct (AMREP), Commercial Road, Melbourne, 3004 Victoria, Australia. Jennifer.Wilkinson-Berka@monash.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Wilkinson-Berka
authors.forename: G
authors.initials: G
authors.lastname: Tan
authors.forename: K J
authors.initials: KJ
authors.lastname: Binger
authors.forename: L
authors.initials: L
authors.lastname: Sutton
authors.forename: K
authors.initials: K
authors.lastname: McMaster
authors.forename: D
authors.initials: D
authors.lastname: Deliyanti
authors.forename: G
authors.initials: G
authors.lastname: Perera
authors.forename: D J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: A G
authors.initials: AG
authors.lastname: Miller
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified; D003930:Diabetic Retinopathy / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D017706:Lisinopril / Q000627:therapeutic use; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D017706:Lisinopril; D010100:Oxygen; D012083:Renin; D000092502:Renin Inhibitors; C473112:Ren2 protein, mouse; C446481:aliskiren