May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Reduction of Experimental Diabetic Vascular Leakage by Delivery of Angiostatin With a Recombinant Adeno-Associated Virus Vector
M. P. Shyong; F.-L. Lee; P.-C. Kuo; A.-C. Wu; H.-C. Cheng; S.-L. Chen; T. Tung; Y.-P. Tsao
Author Affiliations & Notes
  • M. P. Shyong
    Ophthalmology, Su-Ao Veterans Hosp, Taipei, Taiwan
    Institutie of clinical medicine, national yang-Ming University, Taipei, Taiwan
  • F.-L. Lee
    Ophthalmology, taipei Veterans general Hosp, Taipei, Taiwan
  • P.-C. Kuo
    Medical research, Mackay memorial Hosp, Taipei, Taiwan
  • A.-C. Wu
    Ophthalmology, Mackay memorial Hosp, Taipei, Taiwan
  • H.-C. Cheng
    Ophthalmology, Mackay memorial Hosp, Taipei, Taiwan
  • S.-L. Chen
    Microbiology, National Taiwan University, Taipei, Taiwan
  • T. Tung
    Medicine research and education, Cheng Hsin rehabilitation medical center, Taipei, Taiwan
  • Y.-P. Tsao
    Ophthalmology, mackay memorial Hosp, Taipei, Taiwan
  • Footnotes
    Commercial Relationships M.P. Shyong, None; F. Lee, None; P. Kuo, None; A. Wu, None; H. Cheng, None; S. Chen, None; T. Tung, None; Y. Tsao, None.
  • Footnotes
    Support NSC 94-2314-B-95-002, NSC 95-3112-B-195-001, MMH-E-95006, MMH-9501
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1366. doi:
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      M. P. Shyong, F.-L. Lee, P.-C. Kuo, A.-C. Wu, H.-C. Cheng, S.-L. Chen, T. Tung, Y.-P. Tsao; Reduction of Experimental Diabetic Vascular Leakage by Delivery of Angiostatin With a Recombinant Adeno-Associated Virus Vector. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1366.

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Abstract

Purpose:: To evaluate the efficacy of recombinant adeno-associated virus (rAAV) vector expressing mouse angiostatin (Kringle domains 1 to 4) in reducing retinal vascular leakage in an experimental diabetic rat model

Methods:: rAAV-angiostatin was delivered by intravitreal injection to the right eyes of Sprague-Dawley rats. The contralateral eye received an intravitreal injection of rAAV-lacZ. Gene delivery was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Diabetes was induced by intravenous injection of streptozotocin (STZ). Vascular permeability changes were evaluated by extravascular albumin accumulation and leakage of intravenous injected fluorescein isothiocynate-bovine serum albumin (FITC-BSA). Effects of rAAV-angiostatin on expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), occludin and phospho-p42/p44 MAP kinase in retina tissue were analyzed by Western blotting.

Results:: Gene delivery was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Diabetes was induced by intravenous injection of streptozotocin (STZ). Vascular permeability changes were evaluated by extravascular albumin accumulation and leakage of intravenous injected fluorescein isothiocynate-bovine serum albumin (FITC-BSA). Effects of rAAV-angiostatin on expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), occludin and phospho-p42/p44 MAP kinase in retina tissue were analyzed by Western blotting.

Conclusions:: Intravitreal delivery of rAAV-angiostatin reduces vascular leakage in a STZ-induced diabetic model. This effect is associated with a reduction in the retinal occludin loss induced by diabetes, and downregulation of retinal VEGF and phosphor-p42/p44 MAP kinase expression. This gene transfer approach may reduce diabetic macular edema, providing protection in diabetic patients at risk for macular edema

Keywords: gene transfer/gene therapy • diabetic retinopathy • edema 
© 2007, 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 © 2024 Association for Research in Vision and Ophthalmology.
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