May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
VEGF164 is Pro-Inflammatory in the Diabetic Retina
Author Affiliations & Notes
  • S. Ishida
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Univ, Boston, MA, United States
  • T. Usui
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Univ, Boston, MA, United States
  • K. Yamashiro
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Univ, Boston, MA, United States
  • Y. Kaji
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Univ, Boston, MA, United States
  • E. Ahmed
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Univ, Boston, MA, United States
  • K.G. Carrasquillo
    Eyetech Research Center, Woburn, MA, United States
  • S. Amano
    Ophthalmology, Tokyo Univ, Tokyo, Japan
  • T. Hida
    Ophthalmology, Kyorin Univ, Tokyo, Japan
  • Y. Oguchi
    Ophthalmology, Keio Univ, Tokyo, Japan
  • A.P. Adamis
    Ophthalmology, Keio Univ, Tokyo, Japan
  • Footnotes
    Commercial Relationships  S. Ishida, Eyetech F; T. Usui, Eyetech F; K. Yamashiro, Eyetech F; Y. Kaji, Eyetech F; E. Ahmed, Eyetech F; K.G. Carrasquillo, Eyetech E; S. Amano, None; T. Hida, None; Y. Oguchi, None; A.P. Adamis, Eyetech E.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3895. doi:
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    • Get Citation

      S. Ishida, T. Usui, K. Yamashiro, Y. Kaji, E. Ahmed, K.G. Carrasquillo, S. Amano, T. Hida, Y. Oguchi, A.P. Adamis; VEGF164 is Pro-Inflammatory in the Diabetic Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3895.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The objectives of this study were to: (1) characterize the differential potency of two major VEGF isoforms, VEGF120 and VEGF164, for inducing leukocyte stasis (leukostasis) within the retinal vasculature and blood-retinal barrier (BRB) breakdown and (2) determine whether endogenous VEGF164 mediates retinal leukostasis and BRB breakdown in early and established diabetes. Methods: Retinal leukostasis and BRB breakdown were simultaneously quantified by combining Concanavalin A lectin (Con A) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed to confirm that Con A-stained cells within the vasculature were leukocytes. Retinal leukostasis and BRB breakdown were compared in non-diabetic rats receiving intravitreal injections of VEGF120 or VEGF164. Retinal intercellular adhesion molecule-1 (ICAM-1) and VEGF protein levels were studied via Western blot and ELISA, respectively. An anti-VEGF164 (165) aptamer (EYE001) was administered via intravitreal injection to 2-week and 3-month diabetic rats, and the effect on retinal leukostasis and BRB breakdown was quantified. Results: Compared to VEGF120, VEGF164 more potently increased retinal ICAM-1 levels (2.2-fold), leukostasis (1.9-fold) and BRB breakdown (2.1-fold). Retinal leukostasis and leakage increased with the duration of diabetes (P < 0.01), and were closely correlated (P < 0.01, r = 0.889). The isoform-specific blockade of endogenous VEGF164 with EYE001 resulted in a significant suppression of retinal leukostasis and BRB breakdown in both early (72.4% and 82.6%, respectively) and established (48.5% and 55.0%, respectively) diabetes (P < 0.01). Conclusions: On an equimolar basis, VEGF164 is at least twice as potent as VEGF120 at inducing ICAM-1-mediated retinal leukostasis and BRB breakdown in vivo. The inhibition of diabetic retinal leukostasis and BRB breakdown with EYE001 in early and established diabetes indicates that VEGF164 is an important isoform in the pathogenesis of early diabetic retinopathy.

Keywords: diabetic retinopathy • growth factors/growth factor receptors • inflammation 
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