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
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:https://doi.org/
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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. doi: https://doi.org/.

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

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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 
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