May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Attenuating Photoreceptor Apoptosis by Overexpression of Heme Oxygenase-1 in an Experimental Model of Retinal Detachment
M. P. Shyong; F.-L. Lee; W.-H. Hen; P.-C. Kuo; A.-C. Wu; H.-C. Cheng; S.-L. Chen; T.-H. Tung; Y.-P. Tsao
Author Affiliations & Notes
  • M. P. Shyong
    Ophthalmology, Su Ao Veterans Hosp, Taipei, Taiwan
  • F.-L. Lee
    Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
  • W.-H. Hen
    Medical research,
    Mackay Memorial Hospital, Taipei, Taiwan
  • P.-C. Kuo
    Microbiology, National Taiwan University, School of Medicine, Taipei, Taiwan
  • A.-C. Wu
    Ophthalmology,
    Mackay Memorial Hospital, Taipei, Taiwan
  • H.-C. Cheng
    Ophthalmology,
    Mackay Memorial Hospital, Taipei, Taiwan
  • S.-L. Chen
    Microbiology, National Taiwan University, School of Medicine, Taipei, Taiwan
  • T.-H. Tung
    Medicine Research and Education, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan
  • Y.-P. Tsao
    Ophthalmology,
    Mackay Memorial Hospital, Taipei, Taiwan
  • Footnotes
    Commercial Relationships  M.P. Shyong, None; F. Lee, None; W. Hen, None; P. Kuo, None; A. Wu, None; H. Cheng, None; S. Chen, None; T. Tung, None; Y. Tsao, None.
  • Footnotes
    Support  National Science Council, Taiwan (NSC 94 - 2314 - B - 95 - 002, NSC 95 - 3112 - B - 195 - 001), and from the Mackay Memorial Hospital (MMH - E - 95006, MMH - 9501)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5221. doi:
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      M. P. Shyong, F.-L. Lee, W.-H. Hen, P.-C. Kuo, A.-C. Wu, H.-C. Cheng, S.-L. Chen, T.-H. Tung, Y.-P. Tsao; Attenuating Photoreceptor Apoptosis by Overexpression of Heme Oxygenase-1 in an Experimental Model of Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5221.

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Abstract

Purpose: : To evaluate overexpression of heme oxygenase-1(HO-1) on photoreceptor apoptosis in an experimental model of retinal detachment (RD).

Methods: : 5 groups of Sprague-Dawley (SD) rats were studied: normal rats, rats receiving subretinal injection of recombinant adeno-associated virus expressing HO-1 (rAAV-HO-1), rats receiving subretinal rAAV-lacZ injection, rats receiving repeated intraperitoneal cobalt protoporphorin (CoPP, 5 mg/kg) injection, and rats receiving repeated PBS injection. RD was created in right eye after rAAV, CoPP and PBS administration. HO-1 expression was confirmed by immunofluorescence and Western blotting. Apoptotic cells and activation of caspase-3 was studied at 2 days of RD. The preservation of the thickness of photoreceptor outer nuclear layer (ONL) was evaluated at 28 days of RD.

Results: : Both rAAV-HO-1 delivery and CoPP administration lead to HO-1 overexpression. Subretinal rAAV-HO-1 delivery achieves localized high HO-1 gene expression in the ONL while systemic CoPP administration induced a diffuse, moderate expression of HO-1 throughout the retina. ONL thickness in eyes receiving rAAV-HO-1 injection was significantly higher than in rAAV-lacZ-treated or PBS-treated eyes at 28 days of RD, while CoPP treatment did not lead to significant ONL preservation (Kruskal-Wallis test, n = 6, P = 0.01). There were fewer TUNEL-positive cells (Kruskal-Wallis test, n = 5, P = 0.011) and less activated caspase-3 (Kruskal-Wallis test, n = 5, P = 0.011) in rAAV-HO-1 treated eyes than in control eyes, while CoPP had no such effect.

Conclusions: : Both subretinal injection of rAAV-HO-1 and systemic CoPP administration led to the overexpression of HO-1 in the retina. rAAV-HO-1 injection resulted in fewer photoreceptor apoptosis than CoPP administration. This gene transfer approach may be a valuable adjuvant to current treatments for RD.

Keywords: retinal detachment • photoreceptors • gene transfer/gene therapy 
© 2008, 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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