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

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

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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 
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