December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Effects of Tenascin-C on the Angiogenic Potential of Retinal Endothelial Cells
R Castellon; S Caballero; HK Hamdi; AM Aoki; MC Kenney; MB Grant; AV Ljubimov
Author Affiliations & Notes
  • R Castellon
    Ophthalmology Research Laboratories Cedars-Sinai Medical Center Los Angeles CA
  • S Caballero
    Department of Pharmacology University of Florida Gainesville FL
  • HK Hamdi
    Ophthalmology Research Laboratories Cedars-Sinai Medical Center Los Angeles CA
  • AM Aoki
    Ophthalmology Research Laboratories Cedars-Sinai Medical Center Los Angeles CA
  • MC Kenney
    Ophthalmology Research Laboratories Cedars-Sinai Medical Center Los Angeles CA
  • MB Grant
    Department of Pharmacology University of Florida Gainesville FL
  • AV Ljubimov
    Ophthalmology Research Laboratories Cedars-Sinai Medical Center Los Angeles CA
  • Footnotes
    Commercial Relationships   R. Castellon, None; S. Caballero, None; H.K. Hamdi, None; A.M. Aoki, None; M.C. Kenney, None; M.B. Grant, None; A.V. Ljubimov, None. Grant Identification: Support: NIH Grant EY12605
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1328. doi:
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      R Castellon, S Caballero, HK Hamdi, AM Aoki, MC Kenney, MB Grant, AV Ljubimov; Effects of Tenascin-C on the Angiogenic Potential of Retinal Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1328.

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Abstract

Abstract: : Purpose: Tenascin-C (TN-C) is an extracellular matrix protein expressed in embryogenesis and in adult tissues undergoing remodeling and healing. We previously reported that TN-C was upregulated in diabetic retinopathy (DR) human retinas. However, its precise role remained elusive. We hypothesized that TN-C promotes the angiogenic phenotype. Our purpose was to examine TN-C production by retinal endothelial cells (REC) in response to growth factors (GFs) known to be upregulated in DR, as well as the effects of TN-C +/- GFs on various in vitro angiogenic assays. Methods: Bovine and human REC were cultured on plastic and on reconstituted basement membrane matrix (Matrigel). TN-C production, capillary-like tube formation, secondary sprouting, cell migration, survival and proliferation were measured after treatment with combinations of angiogenic growth factors +/- TN-C. The involvement of TN-C integrin receptors on TN-C action was investigated using specific blocking antibodies. Results: TN-C delayed tube collapse of REC on Matrigel in a dose- and time-dependent manner. It also decreased tube collapse induced by serum deprivation, 30 mM glucose and 0.1 nM TGF-ß by 50%, 35% and 85%, with similar effects on REC growing on plastic. This indicates that TN-C exerts some survival effects. TN-C also increased secondary sprouting, REC proliferation, migration and tube branching. αVß3 integrin was important for TN-C action since a blocking antibody to this integrin decreased tube length, network complexity and secondary sprouting by 50%, 35% and 100%. Antibodies against αVß6, αVß5, and α9ß1 integrins had little or no effect. Immunocytochemistry showed that GFs known to be upregulated in DR retinas increased TN-C deposition in an additive or synergistic manner, which may explain why DR cells have higher basal levels of TN-C. Conclusion: TN-C was overexpressed in diabetic and DR REC cultures and was upregulated by GF combinations. TN-C enhanced the angiogenic potential of REC as measured by a variety of in vitro assays. The data suggest that TN-C may act as a pro-angiogenic mediator in DR and other pathological conditions and provide possible avenues for future therapeutic intervention.

Keywords: 566 retinal neovascularization • 423 growth factors/growth factor receptors • 403 extracellular matrix 
© 2002, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2015 Association for Research in Vision and Ophthalmology.
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