May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
The 16 kDa Fragment of Prolactin Modulates Endothelial Cell Apoptosis and In Vivo Retinal Angiogenesis
H. Pan; N. Nguyen; H. Yoshida; F. Bentzien; I. Struman; R. Weiner; M.B. Grant
Author Affiliations & Notes
  • H. Pan
    Pharmacology and Therapeutics, University Florida, Gainesville, FL, United States
  • N. Nguyen
    Lab. Mol. Biology, University of Liege, Sart Tilman, Belgium
  • H. Yoshida
    Dept Ob. Gyn, University of California at San Francisco, San Francisco, CA, United States
  • F. Bentzien
    Dept Ob. Gyn, University of California at San Francisco, San Francisco, CA, United States
  • I. Struman
    Dept Ob. Gyn, University of California at San Francisco, San Francisco, CA, United States
  • R. Weiner
    Dept Ob. Gyn, University of California at San Francisco, San Francisco, CA, United States
  • M.B. Grant
    Dept Ob. Gyn, University of California at San Francisco, San Francisco, CA, United States
  • Footnotes
    Commercial Relationships  H. Pan, None; N. Nguyen, None; H. Yoshida, None; F. Bentzien, None; I. Struman, None; R. Weiner, None; M.B. Grant, None.
  • Footnotes
    Support  The Juvenile Diabetes Research Foundation International; NIH grants EY012601 and EY007739
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 2899. doi:
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      H. Pan, N. Nguyen, H. Yoshida, F. Bentzien, I. Struman, R. Weiner, M.B. Grant; The 16 kDa Fragment of Prolactin Modulates Endothelial Cell Apoptosis and In Vivo Retinal Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2899.

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Abstract

Abstract: : Purpose: The 16 kDa fragment of human prolactin (16K hPRL) is a potent specific antiangiogenic factor in vivo and in vitro. 16K hPRL inhibits VEGF- and bFGF-induced capillary endothelial cell growth by blocking activation of the MAPK signaling cascade and inducing apoptosis. However, the effect of 16K hPRL on vascular cells of the retina has not been evaluated. We compared the effect of 16K hPRL to the potent antiangiogenic agent endostatin on human retinal endothelial cell (HREC) apoptosis and evaluated the effect of 16K hPRL on retinal neovascularization using the mouse model of ischemia-induced retinopathy. Methods: Varying concentration (5, 10, and 20 nM) of 16K hPRL were added to HREC and the level of DNA fragmentation associated with apoptosis was evaluated by measuring the levels of cytosolic mono- and oligonucleosomes using an ELISA assay. The 16K hPRL-encoding sequence was inserted into an adenovirus vector (Ad-16K) and expression of the secreted form of 16K hPRL was verified by Western analysis following infection of HCT116 cells. Ad-16K or Ad-null vectors were intravitreally injected in one-day-old mice. The mice were then subjected to the neonatal oxygen induced retinopathy model. Eyes were sectioned and neovascularization scored by light microscopy. Results: 16K hPRL activated HREC apoptosis and the effect of 5 nM 16K hPRL was comparable to that seen with 0.5 µM endostatin. Eyes injected with Ad-16K showed a reduction in pre-retinal neovascularization of 59.7 ± 20.0% (p=4.1X10-10) when compared to uninjected controls, while eyes injected with Ad-Null showed no significant difference when compared to uninjected controls (p=0.3). Conclusions: 16K hPRL is a potent apoptotic agent in HREC. Using a gene therapy approach 16K hPRL effectively inhibits retinal neovascularization in the mouse model of ischemia-induced retinopathy. These findings support the potential of 16 K hPRL as a therapeutic agent for treatment of proliferative retinopathies.

Keywords: diabetic retinopathy • iris • retinal neovascularization 
© 2003, 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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