Replies to post #1082 on Biotech Values

[DewDiligence]

Another ISOPT paper by Dr. de Juan:

[Moral: don’t forget your tofu!]

http://www.kenes.com/isopt/inv_abstracts/De_Juan1.doc

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GENISTEIN SOY BASED TKI FOR RETINAL PROTECTION

E. De Juan, Jr.1, M. Mahmoud1, M. Cooney2, J. Cao3, R. Grebe4

1Ophthalmology, University of Southern California, Doheny Retina Institute, USA 2Ophthalmology, Duke University School of Medicine, Durham, USA 3Regeneron Pharmaceuticals Inc., Tarrytown, USA 4Wilmer Ophthalmological Institute, Johns Hopkins School of Medicine, Baltimore, USA

Background: Genistein is an isolflavone present abundantly in soybeans. Tyrosine kinase (TK) is pivotal in angiogenesis cascade and genistein is a selective inhibitor of receptor and cytoplasmic TK. Inhibition of TK ameliorated retinal vascular changes in streptozotocin diabetic rat.

Aims: In this study, we investigated the effect of oral genistein on retinal vasculature and neovascularization growth factors in Zucker Diabetic Fatty rats.

Methods: Male Zucker rats (37 diabetic and 39 nondiabetic) were used in this study. The diabetic and nondiabetic rats were each divided into four groups. Genistein-enriched purina (75, 150 and 300 mg/kg food) or regular purina were fed to the assigned group of rats ad libitum and sacrificed at 6 months. Retinal vasculature was examined by flatmount technique using high molecular weight FITC-dextran. Retinovascular leakage was measured by radiolabeled sucrose given IV. Retinas were dissected for immunoblot analysis to detect VEGF, bFGF and phosphorylation of tyrosine-proteins, Flk-1 and MAPK.

Results: Significant decrease (P < 0.05) in diameter of retinal vessels in genistein treated and untreated rats, 5.25+/-1.48 μm and 6.53+/-1.83 μm respectively. Genistein inhibited the phosphorylation of tyrosine-protein and MAPK but it did not affect the expression of VEGF, bFGF and Flk-1 in Zucker diabetic rats. Most interestingly, there was a significant decrease in retinal vascular leakage of labeled sucrose in animals treated with oral genistein.

Conclusion: Genistein ameliorated retinal vascular dilatation and leakage in the Zucker diabetic rat. It also inhibits phosphorylation of tyrosine- protein and MAPK. This inhibition could be through inhibiting protein tyrosine kinase.
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