Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage

Microvasc Res. 2011 Nov;82(3):346-50. doi: 10.1016/j.mvr.2011.09.001. Epub 2011 Sep 16.

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.

Conclusion: Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Blood Glucose / metabolism
  • Blood Proteins / metabolism
  • Blood-Retinal Barrier / drug effects*
  • Blood-Retinal Barrier / enzymology
  • Body Weight
  • Capillary Permeability / drug effects*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetic Retinopathy / enzymology
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / prevention & control*
  • Indazoles
  • Leukocytes / drug effects
  • Leukocytes / enzymology
  • Leukostasis / enzymology
  • Leukostasis / etiology
  • Leukostasis / prevention & control*
  • Macular Edema / enzymology
  • Macular Edema / etiology
  • Macular Edema / prevention & control*
  • Male
  • Molecular Targeted Therapy
  • Ophthalmic Solutions
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Inbred BN
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Time Factors
  • Vitreous Body / metabolism

Substances

  • Blood Glucose
  • Blood Proteins
  • Indazoles
  • Ophthalmic Solutions
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Protein-Tyrosine Kinases