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DIABETIC RETINOPATHY: Tenascin-C contributes to diabetic pathology in eyes.





September 20, 2002.

By Sonia Nichols,
Angiogenesis Weekly.




Researchers have identified a protein that contributes to the pathogenesis of diabetic retinopathy by stimulating neovascularization.


The protein, an angiogenesis modulator, is tenascin-C, and according to researchers in the U.S., it modulates a variety of physiological processes.


"Tenascin-C is expressed in embryogenesis, tissue remodeling, and healing. It is upregulated in retinas of patients affected by diabetic retinopathy," explained Raquel Castellon and colleagues, Cedars-Sinai Medical Center, University of California Los Angeles Medical School, Los Angeles, California. Because diabetic retinopathy is an outgrowth of retinal angiogenesis, or neovascularization, researchers investigated the effects of tenascin-C (TN-C) on bovine and human retinal endothelial cells (REC) growing in culture on plastic or basement membrane matrices. RECs overproliferate in patients with uncontrolled diabetes.


Castellon and colleagues exposed the cells to serum deprivation, high glucose, and transforming growth factor (TGF)-B , elements that would normally cause tube involution. Despite these exposures, TN-C caused decreased tube involution. In the presence of alpha(v)beta(3) integrin, a neovascular promoter, tube stability increased with TN-C.


"TN-C increased REC viability in 0.5% serum and stimulated REC proliferation in 10% serum," Castellon and coauthors described.


Vascular endothelial growth factor, an angiogenic protein also indicted in diabetic retinopathy, worked in concert with TN-C to stimulate more tube branching in cells cultivated on basement membrane matrices. TN-C treatment increased REC sprouting and doubled their migration capacity (Effects of tenascin-C on normal and diabetic retinal endothelial cells in culture, Investigative Ophthalmology and Visual Science, 2002;2758-2766).


"Angiogenic growth factor increased TN-C production by REC in an additive manner, which may explain higher levels of TN-C deposition in diabetic retinopathy cells," the team offered.


By augmenting the ability of angiogenic growth factors to control endothelial cell viability, migration, and sprouting, TN-C may influence the course of diabetic retinopathy as well as other diseases stemming from too much neovascularization.


The corresponding author for this study is Raquel Castellon, Ophthalmology Research Laboratories, Burns and Allen Research Institute, Cedars-Sinai Medical Center, University of California Los Angeles Medical School Affiliate, Los Angeles, CA, USA.


Key points reported in this study include:


*Tenascin-C is a proangiogenic mediator of several physiological processes such as embryogenesis


*Retinal endothelial cells grown in the presence of tenascin-C experienced increased sprouting, migration, and viability


*Tenascin-C augments the effect of angiogenic growth promoters






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