title: Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509.
abstract: OBJECTIVE
  To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications.
  
  
  METHODS
  Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch of 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression of cataracts was monitored by slit-lamp biomicroscopy. After duration of 4, 8, 16, and 24 months, levels of plasma glucose and glycated hemoglobin, as well as erythrocyte and retinal galactose and galactitol, were measured in rats in each group. Retinal vasculatures of the 24-month rats were isolated by elastase digestion and analyzed by computer-assisted morphometry.
  
  
  RESULTS
  Mature, diabetic-like cataracts developed within 5 weeks in all the galactose-fed, untreated rats, but only nonprogressive anterior cortical opacities were present in lenses of 85% of the ARI-treated galactosemic animals after 3 months. Plasma glucose remained the same in all groups. Erythrocyte and retinal galactose and glycated (galactosylated) hemoglobin were elevated with galactosemia and were unaffected by ARI treatment. Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment. At 24 months, capillary length, width, density, the number of microaneurysms, and the percent of capillary length involved in intraretinal microvascular abnormalities, expressed as hypercellular channels with diameters > 20 microns, were significantly increased by galactosemia and were attenuated in the galactose-fed, ARI-treated group.
  
  
  CONCLUSIONS
  A dose of WAY-121,509 sufficient to reduce retinal polyol levels by 95% ameliorated the development of galactose-induced cataracts and diabetic-like retinopathy but was insufficient to prevent early lens opacifications or all the diabetic-like retinal microangiopathies.
authors.affiliation: National Eye Institute, Bethesda, Maryland 20892-2740, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Robinson
authors.forename: N M
authors.initials: NM
authors.lastname: Laver
authors.forename: J L
authors.initials: JL
authors.lastname: Jacot
authors.forename: J P
authors.initials: JP
authors.lastname: Glover
authors.forename: M D
authors.initials: MD
authors.lastname: Basso
authors.forename: P
authors.initials: P
authors.lastname: Blouin
authors.forename: T C
authors.initials: TC
authors.lastname: Hohman
mesh_terms: D000449:Aldehyde Reductase / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D004376:Galactitol / Q000378:metabolism; D005690:Galactose; D006442:Glycated Hemoglobin / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007908:Lens, Crystalline / Q000187:drug effects / Q000503:physiopathology; D011108:Polymers / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology
chemical_list: D000449:Aldehyde Reductase; D001786:Blood Glucose; D004376:Galactitol; D005690:Galactose; D006442:Glycated Hemoglobin; D011108:Polymers; C091470:WAY 121-509; C024617:polyol