Normalization of retinal vascular permeability in experimental diabetes with genistein.

Publication: Investigative ophthalmology & visual science
Publication Date: 2001
Study Author(s): Nakajima, M;Cooney, M J;Tu, A H;Chang, K Y;Cao, J;Ando, A;An, G J;Melia, M;de Juan, E;
Institution: Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
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PURPOSE : To study the effects of genistein, a Tyrosine kinase inhibitor, on retinal vascular permeability in an experimental diabetic rat model.

METHODS : Seventy-two rats were equally divided into four groups: (1) nondiabetic control group, (2) diabetic control group, (3) diabetic rats receiving 150 mg genistein/kg food, and (4) diabetic rats receiving 300 mg genistein/kg food. diabetes was induced by streptozotocin injection in the three diabetic groups. Rats were fed diets with or without Genistein and followed for 6 months. Retinal vascular permeability was assessed by measuring radiolabeled Sucrose leakage into the retina and by Western blot analysis for total retinal albumin. Retinal phosphotyrosine levels and proliferating cell nuclear antigen (PCNA) were also evaluated by Western blot analysis.

RESULTS : Diabetic control rats had markedly increased retinal vascular leakage of radiolabeled Sucrose compared with nondiabetic control rats. Diabetic rats receiving oral Genistein had significantly less retinal vascular leakage of radiolabeled Sucrose than diabetic control rats in a dose-response fashion. Diabetic control rats had increased levels of phosphotyrosine, retinal albumin, and PCNA by Western blot analysis compared with nondiabetic control rats. Rats receiving 300 mg of genistein had decreased retinal albumin by Western blot analysis. Western blot analysis demonstrated a dose-response decrease in retinal phosphotyrosine levels and PCNA in genistein-treated diabetic rats compared with diabetic control rats.

CONCLUSIONS : Long-term oral administration of genistein significantly inhibits retinal vascular leakage in experimentally induced diabetic rats. Tyrosine kinase inhibition may be a useful pharmacological approach for the treatment of diabetic-induced retinal vascular leakage.
PMID: 11481279

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