title: Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage.
abstract: OBJECTIVE
  To determine the efficacy of pazopanib eye drops in the streptozotocin induced diabetic retinopathy rat model.
  
  
  METHODS
  A 0.5% w/v pazopanib suspension was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5% w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three groups (n=4) - (1) healthy, (2) diabetic, and (3) diabetic with treatment. The drug suspension was administered twice daily as eye drops to group 3 for 30 days. Efficacy parameters including the number of adherent leukocytes in the retinal vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to-plasma protein ratio were measured.
  
  
  RESULTS
  Pazopanib suspension in the form of eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%), and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to untreated diabetic group.
  
  
  CONCLUSIONS
  Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.
authors.affiliation: Nanomedicine and Drug Delivery Laboratory, Department of Pharmaceutical Sciences, Aurora, CO 80045, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Thakur
authors.forename: Robert I
authors.initials: RI
authors.lastname: Scheinman
authors.forename: Vidhya R
authors.initials: VR
authors.lastname: Rao
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000201:enzymology; D001835:Body Weight; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D007191:Indazoles; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D018921:Leukostasis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008269:Macular Edema / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D058990:Molecular Targeted Therapy; D009883:Ophthalmic Solutions; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D007191:Indazoles; D009883:Ophthalmic Solutions; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases